IRS-1

Summary

Gene Symbol: IRS-1
Description: insulin receptor substrate 1
Alias: HIRS-1, insulin receptor substrate 1, IRS-1
Species: human

Top Publications

  1. doi Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women
    Alain Veilleux
    Molecular Endocrinology and Oncology Research Center, Laval University, Quebec, Quebec, Canada G1V 4G2
    Metabolism 58:624-31. 2009
  2. ncbi The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms
    Valerio Pazienza
    Division of Clinical Pathology, University Hospital, Geneva, Switzerland
    Hepatology 45:1164-71. 2007
  3. ncbi T-antigen of the human polyomavirus JC attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51
    Joanna Trojanek
    Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Biology Life Science Building, Philadelphia, Pennsylvania 19122, USA
    J Cell Physiol 206:35-46. 2006
  4. pmc TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis
    Youde Jiang
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Cell Signal 24:1086-92. 2012
  5. pmc The induction of microRNA targeting IRS-1 is involved in the development of insulin resistance under conditions of mitochondrial dysfunction in hepatocytes
    Hyun Su Ryu
    Department of Biochemistry, Dongguk University College of Medicine, Kyungju, Korea
    PLoS ONE 6:e17343. 2011
  6. ncbi Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2
    Takumi Kawaguchi
    Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan
    Am J Gastroenterol 102:570-6. 2007
  7. ncbi Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2
    Nanao Horike
    Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Biol Chem 278:18440-7. 2003
  8. ncbi Energy depletion inhibits phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794
    Alexandros Tzatsos
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    J Biol Chem 282:18069-82. 2007
  9. ncbi Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus
    K Almind
    Steno Diabetes Center, Copenhagen, Gentofte, Denmark
    Lancet 342:828-32. 1993
  10. ncbi The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer
    Kerstin Wagner
    Division of Molecular Genetic Epidemiology C050, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Carcinogenesis 25:2473-8. 2004

Research Grants

  1. Morris F White; Fiscal Year: 2014
  2. Gene and environment interaction and insulin resistance
    Raquel Villegas; Fiscal Year: 2013
  3. George L King; Fiscal Year: 2016
  4. Mechanisms of S6K1 Mediated Insulin Resistance
    George Thomas; Fiscal Year: 2010
  5. Aging, Inflammation and Exercise in Chronic Stroke
    Alice S Ryan; Fiscal Year: 2012
  6. Steroid regulation of glucose utilization during early pregnancy.
    ANTONINA I FROLOVA; Fiscal Year: 2010
  7. Ashok Kumar; Fiscal Year: 2016
  8. Morris F White; Fiscal Year: 2016
  9. The In Vivo Role of JNK-1 and IRS-1 Ser307 Phosphorylation In Development of Insu
    Umut Ozcan; Fiscal Year: 2012
  10. Neelima Chauhan; Fiscal Year: 2014

Detail Information

Publications255 found, 100 shown here

  1. doi Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women
    Alain Veilleux
    Molecular Endocrinology and Oncology Research Center, Laval University, Quebec, Quebec, Canada G1V 4G2
    Metabolism 58:624-31. 2009
    ..This divergent pattern of expression may reflect a lower capacity of omental adipose tissue to respond to insulin stimulation at all adiposity levels...
  2. ncbi The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms
    Valerio Pazienza
    Division of Clinical Pathology, University Hospital, Geneva, Switzerland
    Hepatology 45:1164-71. 2007
    ..We measured the expression levels of insulin receptor substrate 1 (IRS-1), IRS-2, and other factors involved in the insulin signal pathway in a human hepatoma cell line (..
  3. ncbi T-antigen of the human polyomavirus JC attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51
    Joanna Trojanek
    Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Biology Life Science Building, Philadelphia, Pennsylvania 19122, USA
    J Cell Physiol 206:35-46. 2006
    ..T-antigen does not operate directly but utilizes a cytosolic molecule, insulin receptor substrate 1 (IRS-1)...
  4. pmc TNFα and SOCS3 regulate IRS-1 to increase retinal endothelial cell apoptosis
    Youde Jiang
    Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Cell Signal 24:1086-92. 2012
    ..Resolution of the hyperglycemia-induced TNFα levels in retinal endothelial cells may prevent apoptosis through disinhibition of insulin receptor signaling...
  5. pmc The induction of microRNA targeting IRS-1 is involved in the development of insulin resistance under conditions of mitochondrial dysfunction in hepatocytes
    Hyun Su Ryu
    Department of Biochemistry, Dongguk University College of Medicine, Kyungju, Korea
    PLoS ONE 6:e17343. 2011
    ....
  6. ncbi Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2
    Takumi Kawaguchi
    Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan
    Am J Gastroenterol 102:570-6. 2007
    ..The aim of this study is to examine the effects of clearance of HCV on insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate (IRS)1/2, central molecules for insulin signaling...
  7. ncbi Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2
    Nanao Horike
    Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Biol Chem 278:18440-7. 2003
    ....
  8. ncbi Energy depletion inhibits phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794
    Alexandros Tzatsos
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    J Biol Chem 282:18069-82. 2007
    ..These data define a novel pathway that cooperates with other adaptive mechanisms to formulate the cellular response to energy depletion...
  9. ncbi Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus
    K Almind
    Steno Diabetes Center, Copenhagen, Gentofte, Denmark
    Lancet 342:828-32. 1993
    ..Our results suggest that aminoacid polymorphisms in IRS-1 may be involved in the aetiology of a subset of late-onset NIDDM...
  10. ncbi The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer
    Kerstin Wagner
    Division of Molecular Genetic Epidemiology C050, German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Carcinogenesis 25:2473-8. 2004
    ..54, 95% CI 0.32-0.89, P = 0.01). A genotype combination analysis of the non-synonymous polymorphisms in the IRS1, IRS2 and SHC1 genes did not show any effect on breast cancer risk...
  11. ncbi Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction
    A Kharitonenkov
    Department of Molecular Biology, Max Planck Institut fur Biochemie, Martinsried, Germany
    J Biol Chem 270:29189-93. 1995
    ..The formation of a multiprotein signaling complex involving the insulin receptor, PTP1D, and IRS-1 enhances cellular glucose uptake, a critical process in the physiological action of insulin...
  12. ncbi Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain
    M M Zhou
    Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA
    Nat Struct Biol 3:388-93. 1996
    ..We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments...
  13. ncbi Attenuation of insulin-stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes
    Anna Danielsson
    Department of Cell Biology and Diabetes Research Centre, Linkoping University, SE58185 Linköping, Sweden
    J Biol Chem 280:34389-92. 2005
    ..2 nM with a t(1/2) of about 2 min. The amount of IRS1 was similar in cells from non-diabetic and diabetic subjects. These findings identify a molecular mechanism for insulin resistance in non-selected patients with type 2 diabetes...
  14. pmc Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer
    Ilenia Migliaccio
    Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, BCM 600, Room N1110, Houston, TX 77030, USA
    Breast Cancer Res Treat 123:651-60. 2010
    ..0001) when compared with patients with PR-/IRS-1- tumors. In conclusion, nuclear IRS-1 may be a useful marker to predict tamoxifen response in patients with early breast cancer, particularly when assessed in combination with PR...
  15. pmc Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
    Katsutaro Morino
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536 8012, USA
    J Clin Invest 115:3587-93. 2005
    ....
  16. pmc TBC1D3, a hominoid-specific gene, delays IRS-1 degradation and promotes insulin signaling by modulating p70 S6 kinase activity
    Marisa J Wainszelbaum
    Department of Cell Biology and Physiology, corrected Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS ONE 7:e31225. 2012
    ..These findings suggest that TBC1D3 plays an unanticipated and potentially unique role in the fine-tuning of insulin/IGF-1 signaling, while providing novel insights into the regulation of tumorigenesis by a hominoid-specific protein...
  17. ncbi PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities
    G Wolf
    Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 270:27407-10. 1995
    ..Shc and IRS-1 are phosphorylated by distinct but overlapping sets of receptor-linked tyrosine kinases. These differences may be accounted for by the inherent specificities of their respective PTB domains...
  18. ncbi Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle
    ZhengPing Yi
    Center for Metabolic Biology, Arizona State University, Tempe, AZ 85287 3704, USA
    Diabetes 56:1508-16. 2007
    ..Serine/threonine phosphorylation of IRS-1 is affected by many factors, including insulin. The purpose of this study was to perform global assessment of phosphorylation of serine/threonine residues in IRS-1 in vivo in humans...
  19. ncbi The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation
    X J Sun
    Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA
    J Biol Chem 271:10583-7. 1996
    ..By comparison with the insulin receptor, p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. These results outline a role for p59fyn or other related Src-kinases during insulin and cytokine signaling...
  20. pmc Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1)/suppressor of cytokine signaling 1 (SOCS1) inhibits insulin signal transduction pathway through modulating insulin receptor substrate 1 (IRS-1) phosphorylation
    Y Kawazoe
    Department of Medicine III, Osaka University Medical School, Osaka, Japan
    J Exp Med 193:263-9. 2001
    ..While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin...
  21. ncbi Insulin-like growth factor I receptor signaling and nuclear translocation of insulin receptor substrates 1 and 2
    Hongzhi Sun
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Endocrinol 17:472-86. 2003
    The insulin receptor substrate 1 (IRS-1) can translocate to the nuclei and nucleoli of several types of cells...
  22. ncbi LEPR, ADBR3, IRS-1 and 5-HTT genes polymorphisms do not associate with obesity
    Hatice Mergen
    Department of Molecular Biology, Faculty of Science, Hacettepe University, Ankara, Turkey
    Endocr J 54:89-94. 2007
    ..Weak, though significant, association coefficients obtained with HTT and LEPR loci indicate that the genotype numbers at these loci may depend on BMI status to some extent...
  23. pmc AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation
    Junyu Ning
    Department of Medicine, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27705, USA
    Mol Endocrinol 24:1218-29. 2010
    ..Because IGF-I is an important stimulant of the anabolic response, this effect of AMPK could account for part of its inhibitory effect on protein synthesis, thus allowing more efficient energy use by other cellular processes...
  24. ncbi Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system
    S Tartare-Deckert
    INSERM U145, Nice, France
    J Biol Chem 270:23456-60. 1995
    ..Finally, our data highlight the crucial role of the juxtamembrane domain in signaling by both the IR and the IGF-IR...
  25. ncbi Phosphorylation of insulin receptor substrate-1 (IRS-1) by protein kinase B positively regulates IRS-1 function
    K Paz
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 274:28816-22. 1999
    ..These findings implicate PKB as a positive regulator of IRS-1 functions...
  26. pmc Phosphorylation of human insulin receptor substrate-1 at Serine 629 plays a positive role in insulin signaling
    Moulun Luo
    Center for Metabolic Biology, College of Liberal Arts and Sciences, Tempe, AZ 85287 3704, USA
    Endocrinology 148:4895-905. 2007
    ..Understanding the complex phosphorylation patterns of IRS-1 is crucial to elucidating the factors contributing to insulin resistance and, ultimately, the pathogenesis of type 2 diabetes...
  27. pmc Insulin-like growth factor-1- and interleukin-6-related gene variation and risk of multiple myeloma
    Brenda M Birmann
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 18:282-8. 2009
    ..Nonetheless, the data are consistent with the hypothesis that IGF-1- and IL-6-related gene variation influences susceptibility to multiple myeloma and warrant confirmation in larger populations...
  28. ncbi Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes
    Karim Bouzakri
    INSERM U449 and CRNHL, IFR 62, R Laennec Medical Faculty, F 69370 Lyon Cedex 08, France
    Diabetes 52:1319-25. 2003
    ..Moreover, increased MAPK activity seems to play a role in the phosphorylation of IRS-1 on serine residue in human muscle cells...
  29. ncbi Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10
    B R Dey
    Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Endocrinol 10:631-41. 1996
    ..Coexpression of LexA-IGFIR beta with Ad-Grb10 resulted in strong activation of both LacZ and LEU2 reporter genes; this interaction was dependent upon a tyrosine kinase-active receptor but did not require tyrosine 950...
  30. ncbi Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins
    I Mothe
    Institut National de la Santé et de la Recherche Médicale U145, Nice, France
    Mol Endocrinol 11:1911-23. 1997
    ..Taken together, our results show that p55PIK interacts with key elements in the IGF-I signaling pathway, and that these interactions are negatively modulated by PI 3-kinase itself, providing circuitry for regulatory feedback control...
  31. ncbi Protein-tyrosine phosphatase PTPL1/FAP-1 triggers apoptosis in human breast cancer cells
    Guillaume Bompard
    INSERM, Unit 540, Molecular and Cellular Endocrinology of Cancers, 60 rue de Navacelles, 34090 Montpellier, France
    J Biol Chem 277:47861-9. 2002
    ..Our data therefore suggest new therapeutic routes and strengthen the importance of identifying endogenous regulators and substrates of this phosphatase in breast tumors...
  32. ncbi Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells
    Francesco Andreozzi
    Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro Magna Graecia, Via Tommaso Campanella, 115, 88100 Catanzaro, Italy
    Endocrinology 145:2845-57. 2004
    ..These changes result in impaired coupling of IRS-1 and PI 3-kinase, and activation of the Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway...
  33. ncbi Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries
    H W Yen
    Department of Obstetrics and Gynecology, Cedars Sinai Burns and Allen Research Institute, Cedars Sinai Medical Center The David Geffen School of Medicine at UCLA, 8700 Beverly Blvd, Davis 2066, Los Angeles, CA 90048, USA
    Mol Hum Reprod 10:473-9. 2004
    ....
  34. ncbi Impaired endothelial function in never-treated hypertensive subjects carrying the Arg972 polymorphism in the insulin receptor substrate-1 gene
    Francesco Perticone
    Department of Experimental and Clinical Medicine, G Salvatore University Magna Graecia of Catanzaro, Policlinico Mater Domini Via Tommaso Campanella, 88100 Catanzaro, Italy
    J Clin Endocrinol Metab 89:3606-9. 2004
    ..4 vs. 13.3 +/- 3.5 ml/100 ml(-1) of tissue per min(-1)). Our data strongly suggest that, by inducing endothelial dysfunction, the Arg(972) IRS-1 polymorphism may contribute to the genetic predisposition to develop cardiovascular disease...
  35. ncbi Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin II
    Yoshihiro Taniyama
    Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Arterioscler Thromb Vasc Biol 25:1142-7. 2005
    ..Therefore, we examined the effects of chronic angiotensin II treatment on IRS-1 phosphorylation and protein expression in vascular smooth muscle cells (VSMCs)...
  36. ncbi Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kalpha pathway
    Ingeborg Hers
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK
    Blood 110:4243-52. 2007
    ..These results demonstrate that IGF-1 activates the IGF receptor/IRS/PI3K/PKB pathway, and that PI3Kalpha is essential for the potentiatory effect of IGF-1 on platelet responses...
  37. pmc Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR
    Alexandros Tzatsos
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    J Biol Chem 284:22525-34. 2009
    ..Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold-dependent...
  38. doi Subcellular localization of IRS-1 in IGF-I-mediated chondrogenic proliferation, differentiation and hypertrophy of bone marrow mesenchymal stem cells
    Lara Longobardi
    Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7039, USA
    Growth Factors 27:309-20. 2009
    ....
  39. pmc O-linked N-acetylglucosamine modification of insulin receptor substrate-1 occurs in close proximity to multiple SH2 domain binding motifs
    Amanda L Klein
    Department of Molecular and Cellular Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Mol Cell Proteomics 8:2733-45. 2009
    ..These findings suggest that O-GlcNAc modification represents an additional layer of posttranslational regulation that may impact the specificity of effects elicited by insulin and IGF-1...
  40. doi Knockdown of insulin receptor substrate 1 reduces proliferation and downregulates Akt/mTOR and MAPK pathways in K562 cells
    João Agostinho Machado-Neto
    Hematology and Hemotherapy Center University of Campinas Hemocentro Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, Sao Paulo, Brazil
    Biochim Biophys Acta 1813:1404-11. 2011
    ....
  41. pmc Global IRS-1 phosphorylation analysis in insulin resistance
    P Langlais
    Center for Metabolic and Vascular Biology, School of Life Science, Arizona State University, ISTB1, 550 E Orange St, Tempe, AZ 85287, USA
    Diabetologia 54:2878-89. 2011
    ..IRS-1 serine phosphorylation is often elevated in insulin resistance models, but confirmation in vivo in humans is lacking. We therefore analysed IRS-1 phosphorylation in human muscle in vivo...
  42. ncbi Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1
    L S Argetsinger
    Department of Physiology, University of Michigan Medical School, Ann Arbor 48109 0622, USA
    J Biol Chem 270:14685-92. 1995
    ..In the present study, GH is shown to stimulate tyrosyl phosphorylation of insulin receptor substrate 1 (IRS-1), the principle substrate of the insulin receptor...
  43. ncbi Insulin receptor substrate-1 as a signaling molecule for focal adhesion kinase pp125(FAK) and pp60(src)
    P Lebrun
    INSERM U145, Avenue de Valombrose, 06107 Nice Cedex 2, France
    J Biol Chem 273:32244-53. 1998
    ..Considering our results together, we suggest that integrins and insulin/insulin-like growth factor-I receptor signaling pathways converge at an early point in the signaling cascade, which is the IRS-1 protein...
  44. ncbi Frap-dependent serine phosphorylation of IRS-1 inhibits IRS-1 tyrosine phosphorylation
    M E Hartman
    Department of Animal Sciences, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Biochem Biophys Res Commun 280:776-81. 2001
    ....
  45. ncbi A highly conserved NTRK3 C-terminal sequence in the ETV6-NTRK3 oncoprotein binds the phosphotyrosine binding domain of insulin receptor substrate-1: an essential interaction for transformation
    Chris L Lannon
    Department of Pathology, British Columbia Research Institute for Children s and Women s Health and the University of British Columbia, Vancouver, British Columbia V5Z4H4, Canada
    J Biol Chem 279:6225-34. 2004
    ..These findings indicate that EN.IRS-1 complex formation through the NTRK3 C terminus is essential for EN transformation...
  46. ncbi The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships
    D Sisci
    Dipartimento Farmaco Biologico, University of Calabria, Arcavacata di Rende, Cosenza
    Ann Oncol 18:vi81-5. 2007
    b>Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor alpha (ERalpha) and insulin-like growth factor 1 (IGF-1) in breast cancer cells...
  47. doi Insulin receptor substrate (IRS)-2, not IRS-1, protects human neuroblastoma cells against apoptosis
    Bhumsoo Kim
    Department of Neurology, University of Michigan, 5371 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109 2200, USA
    Apoptosis 14:665-73. 2009
    ....
  48. pmc Insulin receptor substrate-1/2 mediates IL-4-induced migration of human airway epithelial cells
    Steven R White
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Am J Physiol Lung Cell Mol Physiol 297:L164-73. 2009
    ..These data demonstrate that IL-4 can accelerate migration of differentiated AEC after injury. This reparative response does not require STAT6 activation, but rather requires IRS-1 and/or IRS-2...
  49. doi Nitric oxide inhibits the proliferation and invasion of pancreatic cancer cells through degradation of insulin receptor substrate-1 protein
    Hiroki Sugita
    Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
    Mol Cancer Res 8:1152-63. 2010
    ..These findings indicate that NO inhibits the proliferation and invasion of pancreatic cancer cells, at least in part, through upregulation of IRS-1 protein degradation and resultant downregulation of the insulin/IGF-I-Akt pathway...
  50. pmc Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with insulin receptor substrate-1 and enhances insulin actions and adipogenesis
    Yusuke Nakatsu
    From the Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1 2 3 Kasumi, Minami Ku, Hiroshima City, Hiroshima 734 8553, Japan
    J Biol Chem 286:20812-22. 2011
    ..Taken together, these observations indicate that Pin1 binds to IRS-1 and thereby markedly enhances insulin action, essential for adipogenesis...
  51. pmc erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines
    Janice M Knowlden
    Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB, UK
    Breast Cancer Res 13:R93. 2011
    Recently we reported that insulin receptor substrate 1 (IRS-1), classically an adaptor protein for the insulin-like growth factor type I receptor (IGF-IR), associates with the epidermal growth factor receptor in oestrogen receptor (ER)-..
  52. doi Hepatitis C core protein impairs insulin downstream signalling and regulatory role of IGFBP-1 expression
    M Alberstein
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    J Viral Hepat 19:65-71. 2012
    ....
  53. pmc Characterization of an interaction between insulin receptor substrate 1 and the insulin receptor by using the two-hybrid system
    T J O'Neill
    Department of Physiology, University of Maryland School of Medicine, Baltimore 21201
    Mol Cell Biol 14:6433-42. 1994
    b>Insulin receptor substrate 1 (IRS-1) is a major substrate of the insulin receptor and has been implicated in insulin signaling...
  54. ncbi The Gly972Arg polymorphism in the insulin receptor substrate-1 gene contributes to the variation in insulin secretion in normal glucose-tolerant humans
    M Stumvoll
    Medical Clinic, Department of Endocrinology, Metabolism, and Pathobiochemistry, University of Tubingen, Germany
    Diabetes 50:882-5. 2001
    ..It is possible that this polymorphism causes insulin resistance at the level of the beta-cell and contributes to the polygenic etiology of type 2 diabetes...
  55. ncbi IRS-1 mediates inhibition of Ca2+ mobilization by insulin via the inhibitory G-protein Gi
    Irlando Andrade Ferreira
    Thrombosis and Haemostasis Laboratory, Department of Hematology, University Medical Center Utrecht, and Institute for Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands
    J Biol Chem 279:3254-64. 2004
    ..We conclude that insulin attenuates platelet functions by interfering with cAMP suppression through IRS-1 and G(i)...
  56. ncbi The Arg972 variant in insulin receptor substrate-1 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes
    Giorgio Sesti
    Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia di Catanzaro Via Tommaso Campanella, 115 88100 Catanzaro, Italy
    Diabetes Care 27:1394-8. 2004
    ..The aim of this study was to investigate whether diabetic patients carrying the Arg(972) insulin receptor substrate-1 (IRS-1) variant are at increased risk for secondary failure to sulfonylurea...
  57. ncbi Identification of phosphorylation sites in insulin receptor substrate-1 by hypothesis-driven high-performance liquid chromatography-electrospray ionization tandem mass spectrometry
    ZhengPing Yi
    School of Life Sciences, Department of Kinesiology, Arizona State University, Tempe, Arizona 85287, USA
    Anal Chem 77:5693-9. 2005
    ..Of these sites, five have not previously been detected by any method and provide novel candidates for identification in cells or in vivo...
  58. ncbi The role of insulin receptor substrate-1 in the oncogenicity of simian virus 40 T antigen
    An Wu
    Thomas Jefferson University, Department of Cancer Biology, Kimmel Cancer Center, Philadelphia, Pennsylvania 19107, USA
    Cell Cycle 7:1999-2002. 2008
    ..Our results indicate that IRS-1 plays a significant role in Tag activation of cell cycle progression genes...
  59. doi SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells
    Marcello Persico
    Internal Medicine and Hepatology Unit, Second University of Naples, Naples, Italy
    Clin Chem Lab Med 47:1217-25. 2009
    ..The goal of this study was to clarify the role of genotype 1b and 2 in the genetic expression of suppressor of cytokine signaling 3 (SOCS3) and insulin receptor substrate 1 (IRS-1).
  60. pmc The double-stranded RNA-dependent protein kinase differentially regulates insulin receptor substrates 1 and 2 in HepG2 cells
    Xuerui Yang
    Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824, USA
    Mol Biol Cell 21:3449-58. 2010
    ..In summary, we found for the first time that initially known as a virus infection response gene, PKR regulates the upstream central transmitters of insulin signaling, IRS1 and IRS2, through different mechanisms...
  61. ncbi Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance
    Avia Herschkovitz
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Faculty of Agricultural, Food, and Environmental Quality, The Hebrew University of Jerusalem, Rehovot, Israel
    J Biol Chem 282:18018-27. 2007
    ..These findings suggest that insulin-stimulated IRS kinases such as PKCzeta overlap with IRS kinases triggered by inducers of insulin resistance, such as IKKbeta, to phosphorylate IRS-1 on common Ser sites...
  62. pmc Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
    Tuomas O Kilpeläinen
    Medical Research Council MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK
    Nat Genet 43:753-60. 2011
    ..Our findings provide new insights into adiposity and insulin resistance...
  63. ncbi 14-3-3beta protein associates with insulin receptor substrate 1 and decreases insulin-stimulated phosphatidylinositol 3'-kinase activity in 3T3L1 adipocytes
    A Kosaki
    Clinical Research Unit, Diabetes Center, Kyoto National Hospital, Fushimi ku, Kyoto 612, Japan
    J Biol Chem 273:940-4. 1998
    ..A significant amount of insulin receptor substrate 1 (IRS-1) was immunodetected in the immunoprecipitate with anti-14-3-3beta antibody at the basal ..
  64. pmc Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin
    M P Playford
    IGF Group, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, United Kingdom
    Proc Natl Acad Sci U S A 97:12103-8. 2000
    ..In conclusion, we have shown that IGF-1 causes tyrosine phosphorylation and stabilization of beta-catenin. These effects may contribute to transformation, cell migration, and a propensity for metastasis in vivo...
  65. ncbi IRS-1 and IRS-2 are recruited by TrkA receptor and oncogenic TRK-T1
    C Miranda
    INSERM Unité 145 and IFR 50, Faculte de Medecine, Nice, France
    J Cell Physiol 186:35-46. 2001
    ..On the whole, our results suggest that IRS-1 and IRS-2 could be substrates of TRK-T1 and TrkA, and hence could participate in their signal generation...
  66. ncbi Structure and autoregulation of the insulin-like growth factor 1 receptor kinase
    S Favelyukis
    Department of Physiology and Biophysics, School of Medicine State University of New York at Stony Brook, Stony Brook, New York 11794, USA
    Nat Struct Biol 8:1058-63. 2001
    ..Although the nucleotide binding cleft is conserved between IGF1RK and the insulin receptor kinase, sequence differences in the nearby interlobe linker could potentially be exploited for anticancer drug design...
  67. ncbi Genetic variants of insulin receptor substrate-1 (IRS-1) in syndromes of severe insulin resistance. Functional analysis of Ala513Pro and Gly1158Glu IRS-1
    D Berger
    University of Cambridge, Department of Medicine and Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, UK
    Diabet Med 19:804-9. 2002
    ..To define further the role of IRS-1 mutations in human syndromes of severe insulin resistance...
  68. ncbi Increased insulin resistance in obese children who have both 972 IRS-1 and 1057 IRS-2 polymorphisms
    Sophie Le Fur
    Department of Pediatric Endocrinology, Hopital Saint Vincent de Paul, Universite Paris V, Paris, France
    Diabetes 51:S304-7. 2002
    ..Our results stress the need for combined genotype analysis when candidate genes are functionally involved in the same pathway...
  69. ncbi Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor
    Kerilyn R Wick
    Department of Pharmacology, The University of Texas Health Science Center, San Antonio 78229, USA
    J Biol Chem 278:8460-7. 2003
    ..We conclude that binding of hGrb10gamma to IR decreases signaling through the IRS/PI 3-kinase/AKT pathway by physically blocking IRS access to IR...
  70. ncbi BCR-ABL binds to IRS-1 and IRS-1 phosphorylation is inhibited by imatinib in K562 cells
    Fabiola Traina
    Hemocentro, Departamento de Clinica Medica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, P O Box 6198, 13083 970 Campinas, SP, Brazil
    FEBS Lett 535:17-22. 2003
    In the present study we used K562 cells to demonstrate that insulin receptor substrate 1 (IRS-1) is expressed and constitutively phosphorylated in BCR-ABL(+) cells...
  71. ncbi Constitutive over-expression of the insulin receptor substrate-1 causes functional up-regulation of Fas receptor
    Marcus Wiedmann
    Department of Medicine, Liver Research Center, Rhode Island Hospital, Brown University School of Medicine, 55 Claverick Street 4th floor, Providence, RI 02903, USA
    J Hepatol 38:803-10. 2003
    ..However, the livers eventually ceased to grow but remained approximately 25% larger than non-Tg livers. We hypothesized that this growth homeostasis was achieved by parallel activation of pro-apoptosis pathways...
  72. pmc Role of the insulin-like growth factor I/insulin receptor substrate 1 axis in Rad51 trafficking and DNA repair by homologous recombination
    Joanna Trojanek
    Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
    Mol Cell Biol 23:7510-24. 2003
    ..This effect involves an interaction between Rad51 and the major IGF-IR signaling molecule, insulin receptor substrate 1 (IRS-1)...
  73. ncbi Analysis of the type 2 diabetes-associated single nucleotide polymorphisms in the genes IRS1, KCNJ11, and PPARG2 in type 1 diabetes
    Christina Eftychi
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U K
    Diabetes 53:870-3. 2004
    ..with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the ..
  74. ncbi IGF-I regulates caveolin 1 and IRS1 interaction in caveolae
    Danilo Panetta
    Department of Endocrinology and Metabolism, University of Genova, Genoa, Italy
    Biochem Biophys Res Commun 316:240-3. 2004
    ..Moreover, IRS1 co-immunoprecipitates with caveolin 1 and the specific phosphocaveolin 1-IRS1 interaction is increased by IGF-I...
  75. ncbi Protein kinase C-zeta-induced phosphorylation of Ser318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine phosphorylation of IRS-1
    Klaus Moeschel
    Department of Internal Medicine IV, Endocrinology, Metabolism, Pathobiochemistry and Clinical Chemistry, University Hospital Tubingen, D 72076 Tubingen, Germany
    J Biol Chem 279:25157-63. 2004
    ..These results, generated in BHK(IR) cells, suggest that phosphorylation of Ser(318) by PKC-zeta might contribute to the inhibitory effect of prolonged hyperinsulinemia on IRS-1 function...
  76. pmc SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin
    Chaojun Duan
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor 48109 0622, USA
    J Biol Chem 279:43684-91. 2004
    ..that SH2-B, a JAK2-interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin...
  77. ncbi Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls
    Gemma Villuendas
    Department of Endocrinology, Hospital Ramon y Cajal, Madrid, Spain
    Hum Reprod 20:3184-91. 2005
    ....
  78. pmc The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex
    Ji Luo
    Department of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    J Cell Biol 170:455-64. 2005
    ..These results suggest a mechanism of signal down-regulation of IRS-1 that is mediated by monomeric p85 through the formation of a sequestration complex between p85 and IRS-1...
  79. ncbi The phosphorylation of Ser318 of insulin receptor substrate 1 is not per se inhibitory in skeletal muscle cells but is necessary to trigger the attenuation of the insulin-stimulated signal
    Cora Weigert
    Department of Internal Medicine IV, University Hospital Tuebingen, Germany
    J Biol Chem 280:37393-9. 2005
    The Ser/Thr phosphorylation of insulin receptor substrate 1 (IRS) is one key mechanism to stimulate and/or attenuate insulin signal transduction...
  80. ncbi Oxygen tension regulates the stability of insulin receptor substrate-1 (IRS-1) through caspase-mediated cleavage
    Sung Gyun Kang
    Laboratory of Biochemical Genetics, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 282:6090-7. 2007
    ..In conclusion, our study elucidates a mechanism by which insulin and IGF-1 signaling can be matched to the oxygen level that is available to support growth and energy metabolism...
  81. ncbi C-reactive protein induces phosphorylation of insulin receptor substrate-1 on Ser307 and Ser 612 in L6 myocytes, thereby impairing the insulin signalling pathway that promotes glucose transport
    C D'Alessandris
    Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy
    Diabetologia 50:840-9. 2007
    ..However, it is unknown whether CRP directly affects insulin signalling action. To this aim, we determined the effects of human recombinant CRP (hrCRP) on insulin signalling involved in glucose transport in L6 myotubes...
  82. ncbi Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes
    J C Florez
    Simches Research Building CPZN 6820, Diabetes Unit Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Diabetologia 50:1209-17. 2007
    ..However, other nearby variants might account for the putative association signal...
  83. doi Phosphorylation of Ser357 of rat insulin receptor substrate-1 mediates adverse effects of protein kinase C-delta on insulin action in skeletal muscle cells
    Rizwana Sanaullah Waraich
    Division of Clinical Chemistry and Pathobiochemistry, University of Tuebingen, Tuebingen, Germany
    J Biol Chem 283:11226-33. 2008
    ..Together, these data suggest that phosphorylation of Ser(357) mediates at least in part the adverse effects of PKC-delta activation on insulin action...
  84. pmc Interaction between simian virus 40 large T antigen and insulin receptor substrate 1 is disrupted by the K1 mutation, resulting in the loss of large T antigen-mediated phosphorylation of Akt
    Yongjun Yu
    Department of Cancer Biology, 314 Biomedical Research Building, 421 Curie Blvd, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 6142, USA
    J Virol 82:4521-6. 2008
    ..suggesting that the effects of TAg originated upstream of PI3K; thus, we examined the requirement for insulin receptor substrate 1 (IRS1), which binds and activates PI3K...
  85. ncbi The polymorphism in insulin receptor substrate-1 gene and birth weight in neonates at term
    Edyta Simońska-Cichocka
    Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland
    Endokrynol Pol 59:212-6. 2008
    ..The aim of our study was to evaluate the association between the Gly972Arg polymorphism in the IRS-1 gene and birth weight in newborn children with adequate gestational age...
  86. pmc No association between a polymorphic variant of the IRS-1 gene and prostate cancer risk
    K Fall
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Prostate 68:1416-20. 2008
    ..We assessed the influence of the most common IRS-1 gene polymorphism (Gly972Arg) on prostate cancer risk, alone and in combination with IGF-1 and other components in the IGF-1 signaling pathway...
  87. pmc Estrogen receptor beta-mediated nuclear interaction between IRS-1 and Rad51 inhibits homologous recombination directed DNA repair in medulloblastoma
    Katarzyna Urbanska
    Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA
    J Cell Physiol 219:392-401. 2009
    ..Expression of ERbeta coincided with nuclear translocation of insulin receptor substrate 1 (IRS-1), which was previously reported to interfere with the faithful component of DNA repair when ..
  88. ncbi G972R IRS-1 variant impairs insulin regulation of endothelial nitric oxide synthase in cultured human endothelial cells
    Massimo Federici
    Department of Medicine and Aging Sciences, Edificio CeSi, Room 271, University of Chieti, Via dei Vestini, 1, 66100 Chieti, Italy
    Circulation 109:399-405. 2004
    ....
  89. ncbi Associations among IRS1, IRS2, IGF1, and IGFBP3 genetic polymorphisms and colorectal cancer
    Martha L Slattery
    Health Research Center, School of Medicine, University of Utah, Salt Lake City, 84108, USA
    Cancer Epidemiol Biomarkers Prev 13:1206-14. 2004
    ..We hypothesize that genetic polymorphisms of insulin receptor substrates (IRS-1 and IRS-2), IGF-I, and IGFBP-3 alter colorectal cancer risk because of their roles in the insulin-related signaling pathway...
  90. ncbi Nuclear insulin receptor substrate 1 interacts with estrogen receptor alpha at ERE promoters
    Catia Morelli
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Oncogene 23:7517-26. 2004
    b>Insulin receptor substrate 1 (IRS-1) is a major signaling molecule activated by the insulin and insulin-like growth factor I receptors...
  91. ncbi Common polymorphisms in the PPARgamma2 and IRS-1 genes and their interaction influence serum adiponectin concentration in young Finnish men
    Firoozeh Mousavinasab
    Department of Public Health Science and General Practice, University of Oulu, Aapistie 1, P O Box 5000, Oulu 90014, Finland
    Mol Genet Metab 84:344-8. 2005
    ..We conclude that the Ala12Ala genotype of PPARgamma2 is associated with elevated adiponectin level, and that the PPARgamma2 and IRS-1 genes have a possible interaction in their effects on adiponectin concentration...
  92. ncbi Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis
    Shannon L Gibson
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cell Cycle 6:631-7. 2007
    ..Understanding how the IRS proteins function in tumor progression is essential for future efforts aimed at developing approaches to target IRS-1 and IRS-2 in a diagnostic or therapeutic manner for the benefit of breast cancer patients...
  93. pmc The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation
    Xinsong Xu
    Department of Oncological Sciences, The Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    Mol Cell 30:403-14. 2008
    ..In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic ..
  94. doi The insulin receptor substrate-1: a biomarker for cancer?
    Renato Baserga
    Thomas Jefferson University, Kimmel Cancer Center, 233 S 10th Street, 624 BLB, Philadelphia, PA 19107, USA
    Exp Cell Res 315:727-32. 2009
    ..In addition, I would like to propose that IRS-1 may have a more general role in cancer, and could be considered as a protein having the opposite effect of tumor suppressors, a sort of anti-p53 molecule...
  95. doi Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study
    Ana I Burguete-Garcia
    Centro de Enfermedades Infecciosas, Instituto Nacional de Salud Publica, Mexico
    Metabolism 59:38-45. 2010
    ..The restriction of including only participants with normal BMI might increase the power to detect genetic determinants of T2D...
  96. ncbi Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
    X J Sun
    Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215
    Nature 352:73-7. 1991
    ..Thus IRS-1 may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism...
  97. pmc The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling
    E Y Skolnik
    New York University Medical Center, Department of Pharmacology, NY 10016
    EMBO J 12:1929-36. 1993
    ..These interactions may play a crucial role in activation of p21ras and the control of downstream effector molecules...
  98. ncbi Involvement of Janus kinases in the insulin signaling pathway
    S Giorgetti-Peraldi
    Institut National de la Santé et de la Recherche Médicale INSERM U145, Faculte de Medecine, Nice, France
    Eur J Biochem 234:656-60. 1995
    ..In conclusion, our results suggest that the JAK proteins could participate in insulin signal transduction, and could therefore constitute an alternative pathway for mediating some of the pleiotropic responses induced by insulin...
  99. ncbi Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor
    P Gual
    Institut National de la Santé et de la Recherche Médicale U 145, Faculte de Medecine, Nice, France
    Endocrinology 139:884-93. 1998
    ....
  100. pmc Insulin-like growth factor I-induced degradation of insulin receptor substrate 1 is mediated by the 26S proteasome and blocked by phosphatidylinositol 3'-kinase inhibition
    A V Lee
    Division of Medical Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78284 7884, USA
    Mol Cell Biol 20:1489-96. 2000
    b>Insulin receptor substrate 1 (IRS-1) is a critical adapter protein involved in both insulin and insulin-like growth factor (IGF) signaling...
  101. ncbi The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)
    V Aguirre
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 275:9047-54. 2000
    ..These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNFalpha on IRS-1 function...

Research Grants62

  1. Morris F White; Fiscal Year: 2014
    ..3. Identify the mTORC1-dependent phosphorylation sites in IRS1 that regulate insulin signaling and glucose tolerance in mice. ..
  2. Gene and environment interaction and insulin resistance
    Raquel Villegas; Fiscal Year: 2013
    ..Findings from this study can be used to aid in the prevention of T2D, since insulin resistance is a reversible condition. ..
  3. George L King; Fiscal Year: 2016
    ....
  4. Mechanisms of S6K1 Mediated Insulin Resistance
    George Thomas; Fiscal Year: 2010
    ..of nutrient satiation and is most likely mediated through the phosphorylation of specific residues on insulin receptor substrate 1 (IRS1)...
  5. Aging, Inflammation and Exercise in Chronic Stroke
    Alice S Ryan; Fiscal Year: 2012
    ..This research will identify a strategy to treat insulin resistance in stroke survivors and establish the biological basis for recommending lifestyle modifications to reduce inflammation and improve the metabolic profile in stroke. ..
  6. Steroid regulation of glucose utilization during early pregnancy.
    ANTONINA I FROLOVA; Fiscal Year: 2010
    ....
  7. Ashok Kumar; Fiscal Year: 2016
    ..Successful completion of this project will provide critical insights about sarcopenia durin aging and type II diabetes and provide novel avenues for therapeutic interventions. ..
  8. Morris F White; Fiscal Year: 2016
    ....
  9. The In Vivo Role of JNK-1 and IRS-1 Ser307 Phosphorylation In Development of Insu
    Umut Ozcan; Fiscal Year: 2012
    ..Our proposal, by using genetically engineered mouse models, aims to investigate the molecular mechanisms of insulin resistance. ..
  10. Neelima Chauhan; Fiscal Year: 2014
    ..If successful, this project has great potential for clinical translation. ..
  11. Role of the KRLB region in regulating IRS2 function
    KATHARINE ELAINE D apos AQUINO; Fiscal Year: 2010
    ..This information could reveal strategies to reverse the negative consequences of impaired insulin signaling and insulin resistance. ..
  12. S6 Kinase, Aging and Age-related Disease
    Brian K Kennedy; Fiscal Year: 2011
    ..We have determined that reduced S6 kinase function leads to lifespan extension in organisms ranging from yeast to mice. In this proposal, we will dissect the mechanisms by which S6 kinase activity accelerates the aging process. ..
  13. JOSE RAUL MERCADO-MATOS; Fiscal Year: 2016
    ..Additionally, our results can provide the rationale for the development of novel therapeutic approaches for the treatment of IRS2-dependent malignancies. ..
  14. PERINATAL METABOLIC AND HORMONAL EFFECTS
    Sherin U Devaskar; Fiscal Year: 2010
    ..The results of our proposed investigations will fill vital gaps in our knowledge and provide the molecular and cellular basis for perinatal nutritional perturbations causing permanent changes in feeding behavior/energy expenditure. ..
  15. Genetic Markers of GIK Effect in Acute Coronary Syndrome in the IMMEDIATE Trial
    Inga Peter; Fiscal Year: 2012
    ..End of Abstract) ..
  16. TBC1D3: A HOMINOID-SPECIFIC GENE THAT REGULATES GROWTH FACTOR RECEPTOR SIGNALING
    Philip D Stahl; Fiscal Year: 2010
    ..TBC1D3 may serve as a model for developing an understanding of the function of human-specific genes in regulating complex signaling pathways. ..
  17. CYPRIAN CONSTANCE ROSSETTO; Fiscal Year: 2014
    ..Additionally we will explore the interaction of UL84 with other viral encoded factors and identify the role of nucleocytoplasmic shuttling in the activity of UL84. ..
  18. Role and Activation Status of IRS1/2 in IL-4-induced Protection from Cell Death.
    HOLLY A PORTER; Fiscal Year: 2010
    ..Understanding the molecular programming of a cell may also allow for the better prediction of a patient's response to treatment. ..
  19. Neuronal mRNA PET Imaging
    Eric Wickstrom; Fiscal Year: 2010
    ..In the future, beyond the scope of this proposal, nuclear medicine imaging of brain cell gene activity in humans might explain why some individuals become addicted more easily than others. ..
  20. Radiohybridization Imaging of HER2 Oncogene to Detect Breast Cancer
    Eric Wickstrom; Fiscal Year: 2010
    ..In the future, imaging multiple breast cancer genes might diagnose estrogen-dependent vs. estrogen-independent breast cancer without an invasive procedure. ..
  21. Interactions between Imidazoline and Insulin Receptors
    Lincoln Edwards; Fiscal Year: 2005
    ..This new knowledge will stimulate further development of these agents. ..
  22. Receptor 'transactivation' in insulin signaling.
    Louis Luttrell; Fiscal Year: 2004
    ..Understanding these mechanisms may lead to pharmacologic approaches to dissociate the potentially harmful proliferative effects of insulin family receptors from their anti-apoptotic and metabolic effects. ..
  23. PP4 and IGF-1 Signaling in Breast Tumorigenesis
    Tse Hua Tan; Fiscal Year: 2006
    ..b>Insulin receptor substrate 1 (IRS-1) is a key intracellular signaling molecule of the IGF-1 pathway that connects the IGF-1 receptor ..
  24. Sonic Hedghog Signaling in Cerebellum Development and Medulloblastoma
    SUSANA PARATHATH; Fiscal Year: 2009
    ..We will analyze the role of CGNP proliferation using in vivo as well as in vitro by culturing CGNPs and treating with Cre to remove IRS1. ..
  25. MOLECULAR GENETICS OF HUMAN CYTOMEGALOVIRUS
    Julie Kerry; Fiscal Year: 2000
    ....
  26. HCMV DNA REPLICATION GENES IDENTIFIED BY TRANSIENT ASSAY
    DAVID ANDERS; Fiscal Year: 1999
    ....
  27. IRS2 function in beta cell physiology
    Morris F White; Fiscal Year: 2010
    ..3. Establish the relation between T-cell infiltration and Irs2 signaling in beta-cells of the NOD mouse. 4. Investigate the mechanism of Irs2-dependent beta-cell regeneration. ..
  28. CYTOMEGALOVIRUS IMMEDIATE EARLY PROTEINS AND VIRION RNAS
    Thomas E Shenk; Fiscal Year: 2010
    ..HCMV replication will be studied in fibroblasts, the cell commonly used to propagate HCMV;endothelial cells and epithelial cells. ..
  29. SYP PHOSPHATASE AND SIGNAL TRANSDUCTION
    Gen Sheng Feng; Fiscal Year: 2000
    ..The PTP might also participate in insulin signaling since it binds to phosphorylated insulin receptor substrate 1 (IRS1) in adipocytes treated with insulin...
  30. ROLE OF SHP-2 IN IRS1-MEDIATED INSULIN/IGF-1 SIGNALING
    Kyle Copps; Fiscal Year: 2003
    ..An ability of IRS-1[-SHP2] to overcome insulin resistance/diabetes in these models will indicate that SHP-2 may be a reasonable drug target for the treatment of type II diabetes. ..
  31. Genetic Epidemiology of Breast Cancer: BRCA1 and BRCA2
    Susan Neuhausen; Fiscal Year: 2007
    ..This information can be used to assist women and their physicians in individual risk assessment, as well as to target women for specific prevention or treatment strategies based on their genetic risk factors. ..
  32. Pharmacogenetics of the acute response to sulfonylurea and metformin treatment in
    Jose Florez; Fiscal Year: 2008
    ..In addition, this pilot study will lay the groundwork for a long-term, outcomes-based pharmacogenetic clinical trial. [unreadable] [unreadable]..
  33. Genetic variation in drug targets for type 2 diabetes
    Jose Florez; Fiscal Year: 2008
    ..This proposal should serve as the foundation for a large pharmacogenomics trial designed to evaluate the feasibility of genetically-tailored therapy in T2DM. ..
  34. HYPERGLYCEMIA AND VASCULAR CELL SIGNALING
    WILLIAM LOWE; Fiscal Year: 2001
    ..Identifying the signaling pathways that mediate the effects of hyperglycemia on vascular cell function is critical to devising means to prevent these changes and their complications, such as atherosclerosis. ..
  35. Hepatic Steatosis Modulation by Apo B Gene Transcription
    JANET DEHOFF SPARKS; Fiscal Year: 2010
    ....
  36. Promoting Islet Transplantation with Synthetic Scaffolds
    WILLIAM LOWE; Fiscal Year: 2004
    ..abstract_text> ..
  37. Relationship of Apo B and BHMT: Nutrition and Physiology
    Janet Sparks; Fiscal Year: 2004
    ..A potential link of two pathways whose products or intermediates are associated with increased cardiovascular disease risk could be established. ..
  38. PDX-1 Expression and Embryonic Stem Cells
    WILLIAM LOWE; Fiscal Year: 2004
    ..Thus, the proposed studies will address novel ways of promoting the differentiation of ES cells into islets with the ultimate goal of enhancing islet cell transplantation. ..
  39. Replication of GWAS for Maternal Glycemia, Birthweight and their Interaction
    WILLIAM LOWE; Fiscal Year: 2009
    ....
  40. Diabetes Genes: Maternal Glycemia and Birth Weight
    WILLIAM LOWE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  41. BIOLOGICAL FUNCTION OF XRCC2 IN RECOMBINATIONAL REPAIR
    Nan Liu; Fiscal Year: 2003
    ..This study will lead to a better understanding of the role of XRCC2 in mammalian HRR and the importance of this pathway in maintaining chromosomal stability. ..
  42. GENE EXPRESSION IN DIABETES BY SUBTRACTIVE CLONING
    C Kahn; Fiscal Year: 2003
    ..In addition, 6 type 2 DM having low S1 and SG on fs-IVGTT will be compared with 6 offspring with high S1 and high SG, and 6 normoglycemic obese will be compared with 6 lean subjects, for differential expression in muscle and fat. ..
  43. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  44. IDENTIFICATION AND STUDY OF PPARgamma-REGULATED GENES
    DOROTHY SEARS; Fiscal Year: 2004
    ..abstract_text> ..
  45. CORTICOSTEROID INDUCED APOPTOSIS IN AIRWAY EPITHELIUM
    Steven White; Fiscal Year: 2002
    ..These data would help lead to new therapeutic ideas and modalities in the treatment of asthma to suppress inflammation while preventing mucosal damage. ..
  46. CONFERENCE ON DIABETES MELLITUS
    C Kahn; Fiscal Year: 2002
    ..Keystone conferences on diabetes have been held every 2-3 years, and have had increasing registration approaching 600 people (when combined with the obesity conference). ..
  47. 7th Intl Symposium-Neurobiology/Neuroendocrinology/Aging
    Andrzej Bartke; Fiscal Year: 2004
    ..We are also seeking support for the presenters of the Special Lecture and the Keynote Lecture who will be traveling to Bregenz from the United States. ..
  48. Sleep, Metabolic, and Cardiovascular Dysfunction in PCOS
    David Ehrmann; Fiscal Year: 2006
    ..In the other, slow wave activity will be suppressed without awakening the subject and REM sleep will be left undisturbed. Each study will be preceded by 2 nights of basetine sleep. ..
  49. The fuel sensing enzyme AMPK in the pathogenesis of prostate cancer
    Zhijun Luo; Fiscal Year: 2010
    ..g. adiponectin and leptin), success in this effort would suggest a novel, yet practical approach for treating prostate cancers in humans. ..
  50. Aging:Mechanisms & Prevention:34th Annual Meeting of AGE
    Andrzej Bartke; Fiscal Year: 2005
    ..Financial assistance will be provided to those in training to encourage their participation in the meeting. ..
  51. Diabetes Genome Anatomy Project (DGAP)
    C Kahn; Fiscal Year: 2006
    ..abstract_text> ..
  52. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  53. Regulation of airway epithelial repair
    Steven R White; Fiscal Year: 2010
    ....
  54. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  55. Feasibility of Rehabilitation Robots and fMRI in Stroke
    A Tzika; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  56. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    FRANCO BATTISTA FOLLI; Fiscal Year: 2010
    ....
  57. Eighth & Ninth International Symposia on Neurobiology & Neuroendocrinology Aging
    Andrzej Bartke; Fiscal Year: 2007
    ..We are also seeking partial support for the expenses of invited speakers from the United States. [unreadable] [unreadable] [unreadable]..
  58. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  59. Serine / Threonine Phosphorylation and IRS1 Degradation
    Nancy Fidyk; Fiscal Year: 2008
    ....
  60. MECHANISM OF RAF-1 ACTIVATION
    Zhijun Luo; Fiscal Year: 2008
    ..These studies will provide new information as to how Raf is activated and how its activation affects cellular functions. They will also serve as a framework for evaluating the role of the Raf family in human malignancy. ..