Genomes and Genes
Gene Symbol: C-kit
Description: KIT proto-oncogene receptor tyrosine kinase
Alias: C-Kit, CD117, PBT, SCFR, mast/stem cell growth factor receptor Kit, c-Kit protooncogene, p145 c-kit, piebald trait protein, proto-oncogene c-Kit, proto-oncogene tyrosine-protein kinase Kit, soluble KIT variant 1, tyrosine-protein kinase Kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene-like protein
- Park S, Chi H, Min S, Park B, Jang S, Park C. Prognostic impact of c-KIT mutations in core binding factor acute myeloid leukemia. Leuk Res. 2011;35:1376-83 pubmed publisher..In patients with inv(16), there was no prognostic impact of c-KIT mutations. Therefore, an analysis of mutKIT17 in adult CBF AML patients with t(8;21) is recommended as a means to predict prognosis. ..
- Herpel E, Jensen K, Muley T, Warth A, Schnabel P, Meister M, et al. The cancer stem cell antigens CD133, BCRP1/ABCG2 and CD117/c-KIT are not associated with prognosis in resected early-stage non-small cell lung cancer. Anticancer Res. 2011;31:4491-500 pubmed..In various tumor entities, expression of cancer stem cell (CSC) antigens has been proven to be prognostically unfavorable. However, for lung cancer, the data are scant and conflicting...
- Hoermann G, Cerny Reiterer S, Perne A, Klauser M, Hoetzenecker K, Klein K, et al. Identification of oncostatin M as a STAT5-dependent mediator of bone marrow remodeling in KIT D816V-positive systemic mastocytosis. Am J Pathol. 2011;178:2344-56 pubmed publisher....
- Fassunke J, Blum M, Schildhaus H, Zapatka M, Brors B, Künstlinger H, et al. qPCR in gastrointestinal stromal tumors: Evaluation of reference genes and expression analysis of KIT and the alternative receptor tyrosine kinases FLT3, CSF1-R, PDGFRB, MET and AXL. BMC Mol Biol. 2010;11:100 pubmed publisher..It remains to be clarified whether an autocrine or paracrine mechanism by overexpression of receptor tyrosine kinase ligands is responsible for the tumorigenesis of wt-GIST. ..
- Wang Y, Zhao L, Wu C, Liu P, Shi L, Liang Y, et al. C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci U S A. 2011;108:2450-5 pubmed publisher..Furthermore, dasatinib prolonged lifespan of mice bearing AE and HyC-KIT N822K-coexpressing leukemic cells and exerted synergic effects while combined with cytarabine, thus providing a potential therapeutic for t(8;21) leukemia. ..
- Zietsch J, Ziegenhagen N, Heppner F, Reuss D, von Deimling A, Holtkamp N. The 4q12 amplicon in malignant peripheral nerve sheath tumors: consequences on gene expression and implications for sunitinib treatment. PLoS ONE. 2010;5:e11858 pubmed publisher..Sunitinib is a drug targeting receptor tyrosine kinases (RTK) like PDGFRalpha, c-Kit and VEGFR-2. These genes are structurally related and cluster on chromosomal segment 4q12...
- Wakita S, Yamaguchi H, Miyake K, Mitamura Y, Kosaka F, Dan K, et al. Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia. Leukemia. 2011;25:1423-32 pubmed publisher..006). We conclude that sensitivity of c-kit mutation detection method is important to predict prognosis for t(8;21) AML. ..
- Kim W, Park M, Kim Y, Tae Y, Yang H, Lee J, et al. MicroRNA-494 downregulates KIT and inhibits gastrointestinal stromal tumor cell proliferation. Clin Cancer Res. 2011;17:7584-94 pubmed publisher..Our findings indicate that miR-494 is a negative regulator of KIT in GISTs and overexpressing miR-494 in GISTs may be a promising approach to GIST treatment. ..
- Andea A, Patel R, Ponnazhagan S, Kumar S, DeVilliers P, Jhala D, et al. Merkel cell carcinoma: correlation of KIT expression with survival and evaluation of KIT gene mutational status. Hum Pathol. 2010;41:1405-12 pubmed publisher..However, we did not identify KIT activating mutations in any of the tumors analyzed. ..
- Wilson T, Maric I, Simakova O, Bai Y, Chan E, Olivares N, et al. Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis. Haematologica. 2011;96:459-63 pubmed publisher..Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity. ..
- Haller F, Cortis J, Helfrich J, Cameron S, Schüler P, Schwager S, et al. Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival. Mod Pathol. 2011;24:248-55 pubmed publisher....
- Ma D, Stence A, Bossler A, Hackman J, Bellizzi A. Identification of KIT activating mutations in paediatric solitary mastocytoma. Histopathology. 2014;64:218-25 pubmed publisher..Paediatric solitary mastocytoma is frequently associated with KIT activating mutations, in keeping with a clonal process. KIT mutational status appears insufficient to explain the divergent biology of childhood and adult-onset disease. ..
- Zheng S, Huang K, Tao D, Pan Y. Gene mutations and prognostic factors analysis in extragastrointestinal stromal tumor of a Chinese three-center study. J Gastrointest Surg. 2011;15:675-81 pubmed publisher..Paraffin-embedded tissues from 25 cases of EGIST were analyzed for CD117, CD34, Ki-67, S-100, smooth muscle actin, and desmin expression by immunohistochemical method...
- Zhang M, Ma Q, Hu H, Zhang D, Li J, Ma G, et al. Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1? under normoxic condition. Cancer Lett. 2011;303:108-17 pubmed publisher..Therefore, our results suggest that the inhibition of both c-kit and HIF-1? may be an effective strategy for pancreatic cancer therapy. ..
- Grabellus F, Worm K, Sheu S, Siffert W, Schmid K, Bachmann H. The prevalence of the c-kit exon 10 variant, M541L, in aggressive fibromatosis does not differ from the general population. J Clin Pathol. 2011;64:1021-4 pubmed publisher..The result classifies the M541L variant of c-kit exon 10 as a single nucleotide polymorphism. Because its prevalence does not differ between the AF and general populations, an association with AF tumourigenesis is unlikely. ..
- Ríos Moreno M, Jaramillo S, Pereira Gallardo S, Vallejo A, Mora M, Garcia Escudero A, et al. Gastrointestinal stromal tumors (GISTs): CD117, DOG-1 and PKC? expression. Is there any advantage in using several markers?. Pathol Res Pract. 2012;208:74-81 pubmed publisher..Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Expression of CD117, DOG1 and PKC? was investigated immunohistochemically in a series of 99 paraffin-embedded GISTs in order to ..
- Burford A, Little S, Jury A, Popov S, Laxton R, Doey L, et al. Distinct phenotypic differences associated with differential amplification of receptor tyrosine kinase genes at 4q12 in glioblastoma. PLoS ONE. 2013;8:e71777 pubmed publisher..Thus we have identified differential patterns of gene amplification and expression of RTKs at the 4q12 locus to be associated with specific phenotypes which may reflect their distinct underlying mechanisms. ..
- Chau W, Ip C, Mak A, Lai H, Wong A. c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/?-catenin-ATP-binding cassette G2 signaling. Oncogene. 2013;32:2767-81 pubmed publisher..The tumor-promoting microenvironment, such as hypoxia, could promote OTICs via upregulation of c-Kit expression. These results unravel an integral role for c-Kit in ovarian neoplastic processes and shed light on its mechanisms of action...
- Krasagakis K, Fragiadaki I, Metaxari M, Kruger Krasagakis S, Tzanakakis G, Stathopoulos E, et al. KIT receptor activation by autocrine and paracrine stem cell factor stimulates growth of merkel cell carcinoma in vitro. J Cell Physiol. 2011;226:1099-109 pubmed publisher..Blockade of KIT and the downstream signaling cascade at various levels results in inhibition of Merkel cell carcinoma growth in vitro, suggesting targets for therapy of this cancer. ..
- Cheng L, Roth L, Zhang S, Wang M, Morton M, Zheng W, et al. KIT gene mutation and amplification in dysgerminoma of the ovary. Cancer. 2011;117:2096-103 pubmed publisher..The purpose of this study was to analyze alterations of the KIT gene in a large series of dysgerminomas and correlate the findings with clinicopathological parameters...
- Chen P, Zong L, Zhao W, Shi L. Efficacy evaluation of imatinib treatment in patients with gastrointestinal stromal tumors: a meta-analysis. World J Gastroenterol. 2010;16:4227-32 pubmed..23 (95% CI: 0.73-2.10, P = 0.44, P(heterogeneity) = 0.42). Most patients with different genotypes of GIST and KIT exon 11-mutant will benefit from the individualized treatment of imatinib. ..
- Regan J, Kendrick H, Magnay F, Vafaizadeh V, Groner B, Smalley M. c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer. Oncogene. 2012;31:869-83 pubmed publisher..The c-Kit signalling network has potential as a target for therapy and/or prevention in BRCA1-associated breast cancer. ..
- El Serafi M, Bahnassy A, Ali N, Eid S, Kamel M, Abdel Hamid N, et al. The prognostic value of c-Kit, K-ras codon 12, and p53 codon 72 mutations in Egyptian patients with stage II colorectal cancer. Cancer. 2010;116:4954-64 pubmed publisher..The authors assessed the prognostic value of c-Kit (also called cluster of differentiation 117 [CD117] or KIT), cyclooxygenase-2 (COX-2), tumor protein 53 (p53), and Kirsten rat sarcoma viral oncogene homolog (K-ras) ..
- Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, et al. Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol. 2011;91:596-602 pubmed publisher..We identified and isolated the tumorigenic cells as CD117(+)Lineage(-) from three different xenografts...
- Kong Y, Si L, Zhu Y, Xu X, Corless C, Flaherty K, et al. Large-scale analysis of KIT aberrations in Chinese patients with melanoma. Clin Cancer Res. 2011;17:1684-91 pubmed publisher..The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry. The most common melanoma subtypes were acral (38.4%) and mucosal (33...
- Gao J, Dang Y, Sun N, Li J, Shen L. C-KIT mutations were closely associated with the response to Imatinib in Chinese advanced gastrointestinal stromal tumor patients. Med Oncol. 2012;29:3039-45 pubmed publisher..C-KIT mutations were closely associated with Imatinib response and progression-free survival of Chinese advanced GIST patients. Other predictive markers for Imatinib would be further investigated. ..
- Novelli M, Rossi S, Rodriguez Justo M, Taniere P, Seddon B, Toffolatti L, et al. DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology. 2010;57:259-70 pubmed publisher..Immunohistochemistry with a panel of antibodies [CD117, DOG1, protein kinase C (PKC)-theta, nestin, CD34, smooth muscle actin (SMA), desmin, S100 and CD171] was ..
- Schoenewolf N, Bull C, Belloni B, Holzmann D, Tonolla S, Lang R, et al. Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations. Eur J Cancer. 2012;48:1842-52 pubmed publisher..P-ERK expression was preferentially found in metastases. KIT mutations predict treatment outcome with KIT inhibitors. Therefore, especially vulvar melanoma patients should be screened for activating KIT mutations. ..
- Pittoni P, Piconese S, Tripodo C, Colombo M. Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors. Oncogene. 2011;30:757-69 pubmed publisher..Here, we summarize the tumor-intrinsic and -extrinsic roles of c-Kit in cancer and discuss TKIs with their on- and off-targets, with a special emphasis on MCs as paradigmatic c-Kit-dependent accomplices for tumor progression. ..
- Soucie E, Hanssens K, Mercher T, Georgin Lavialle S, Damaj G, Livideanu C, et al. In aggressive forms of mastocytosis, TET2 loss cooperates with c-KITD816V to transform mast cells. Blood. 2012;120:4846-9 pubmed publisher..Taken together, these data demonstrate a oncogenic cooperation in mast cells and reveal TET2 mutation as a potential marker to diagnose and predict severe forms of mastocytosis. ..
- Gao X, Lin J, Li Y, Gao L, Wang X, Wang W, et al. MicroRNA-193a represses c-kit expression and functions as a methylation-silenced tumor suppressor in acute myeloid leukemia. Oncogene. 2011;30:3416-28 pubmed publisher..These data reveal a critical role for methylation-repressed miR-193a in myeloid leukemogenesis and the therapeutic promise of upregulating miR-193a expression for c-kit-positive AML. ..
- Ahmad F, D Souza W, Mandava S, Das B. Molecular analysis of WT1 and KIT mutations in patients from an Indian population with de novo acute myeloid leukemia: determination of incidence, distribution patterns, and report of a novel KIT mutation. Leuk Lymphoma. 2011;52:865-76 pubmed publisher..With respect to FLT3 and NPM1 mutations, WT1 was more predominant in FLT3 positive cases and less in NPM1 mutation cases, while no KIT mutation was found in FLT3/NPM1 positive cases. ..
- Molderings G, Meis K, Kolck U, Homann J, Frieling T. Comparative analysis of mutation of tyrosine kinase kit in mast cells from patients with systemic mast cell activation syndrome and healthy subjects. Immunogenetics. 2010;62:721-7 pubmed publisher..The present findings support the idea that the systemic mast cell activation syndrome is a clonal disease most commonly associated with variable activating mutations in the tyrosine kinase kit. ..
- Wallander M, Willmore Payne C, Layfield L. C-KIT and PDGFRA zygosity in gastrointestinal stromal tumors: Correlation with tumor site, tumor size, exon, and CD117 immunohistochemistry. Appl Immunohistochem Mol Morphol. 2011;19:21-7 pubmed publisher..020). Zygosity of C-KIT or PDGFRA mutations did not correlate with most clinicopathologic features of GISTs including tumor size in our subset. However, homozygous mutant GISTs were associated with metastatic disease. ..
- Petrini I, Zucali P, Lee H, Pineda M, Meltzer P, Walter Rodriguez B, et al. Expression and mutational status of c-kit in thymic epithelial tumors. J Thorac Oncol. 2010;5:1447-53 pubmed publisher..No mutations were detected. c-kit expression is strongly but not exclusively related to thymic carcinoma histotype, and it is of prognostic value. Mutations are very rare. ..
- Omholt K, Grafström E, Kanter Lewensohn L, Hansson J, Ragnarsson Olding B. KIT pathway alterations in mucosal melanomas of the vulva and other sites. Clin Cancer Res. 2011;17:3933-42 pubmed publisher....
- Wasag B, Niedoszytko M, Piskorz A, Lange M, Renke J, Jassem E, et al. Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis. Exp Hematol. 2011;39:859-65.e2 pubmed publisher..Finally, our findings support the hypothesis that not only KIT mutations but other additional genetic abnormalities are contributing to more advanced forms of the disease. ..
- Johansson I, Aaltonen K, Ebbesson A, Grabau D, Wigerup C, Hedenfalk I, et al. Increased gene copy number of KIT and VEGFR2 at 4q12 in primary breast cancer is related to an aggressive phenotype and impaired prognosis. Genes Chromosomes Cancer. 2012;51:375-83 pubmed publisher..Increased copy number of VEGFR2 and KIT thus has the potential of functioning as a novel predictive biomarker for selected targeted therapy particularly in the difficult-to-treat TNBC patient category. ..
- Hodi F, Corless C, Giobbie Hurder A, Fletcher J, Zhu M, Mariño Enríquez A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013;31:3182-90 pubmed publisher..Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities...
- Atay S, Banskota S, Crow J, Sethi G, Rink L, Godwin A. Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion. Proc Natl Acad Sci U S A. 2014;111:711-6 pubmed publisher....
- Zong L, Chen P. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumors: a meta-analysis. World J Surg Oncol. 2014;12:71 pubmed publisher..47 (95% CI, 0.25 to 0.90)). KIT mutations, compared with PDGFRA mutations and wild type, represent a poorer prognostic marker in high risk or malignant GISTs. ..
- Nobusawa S, Stawski R, Kim Y, Nakazato Y, Ohgaki H. Amplification of the PDGFRA, KIT and KDR genes in glioblastoma: a population-based study. Neuropathology. 2011;31:583-8 pubmed publisher....
- Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest. 1993;92:1736-44 pubmed..These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells...
- Veiga I, Silva M, Vieira J, Pinto C, Pinheiro M, Torres L, et al. Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline mutation p.Asp820Tyr develop through different cytogenetic progression pathways. Genes Chromosomes Cancer. 2010;49:91-8 pubmed publisher....
- Smalley K, Contractor R, Nguyen T, Xiao M, Edwards R, Muthusamy V, et al. Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase-4 overexpression. Cancer Res. 2008;68:5743-52 pubmed publisher..This group of melanomas may be a subpopulation for which imatinib or other KIT inhibitors may constitute optimal therapy. ..
- Kikuchi H, Yamamoto M, Hiramatsu Y, Baba M, Ohta M, Kamiya K, et al. Effect of loss of heterozygosity of the c-kit gene on prognosis after hepatectomy for metastatic liver gastrointestinal stromal tumors. Cancer Sci. 2007;98:1734-9 pubmed..LOH of the c-kit gene in metastatic liver seems to be a common event, and LOH of the c-kit gene in resected liver GIST may be a helpful factor in the prediction of the post-recurrent prognosis of patients with liver metastasis. ..
- Holtkamp N, Okuducu A, Mucha J, Afanasieva A, Hartmann C, Atallah I, et al. Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity. Carcinogenesis. 2006;27:664-71 pubmed..In summary, PDGFRA, PDGF and KIT dysregulation as well as growth inhibition of cell culture S462 by imatinib may suggest that MPNST patients benefit from treatment with imatinib. ..
- Liu X, Bai C, Xie Q, Feng F, Xu Z, Ma D. Prognostic value of KIT mutation in gastrointestinal stromal tumors. World J Gastroenterol. 2005;11:3948-52 pubmed..C-kit mutation is a undoubtedly pivotal event in GIST and may be associated with poor prognosis. Evaluation of C-kit gene mutation may have both prognosis and therapeutic significances. ..
- Kitamura Y, Hirotab S. Kit as a human oncogenic tyrosine kinase. Cell Mol Life Sci. 2004;61:2924-31 pubmed..The interrelationship between the type of Kit gain-of-function mutations and the therapeutic effect of imatinib mesylate has been well characterized in GISTs. Kit is interesting from both a biological and clinical view-point...
- Beghini A, Magnani I, Ripamonti C, Larizza L. Amplification of a novel c-Kit activating mutation Asn(822)-Lys in the Kasumi-1 cell line: a t(8;21)-Kit mutant model for acute myeloid leukemia. Hematol J. 2002;3:157-63 pubmed....
- Yamazaki K, Sakamoto M, Ohta T, Kanai Y, Ohki M, Hirohashi S. Overexpression of KIT in chromophobe renal cell carcinoma. Oncogene. 2003;22:847-52 pubmed..As overexpression of KIT might be involved in tumor growth, KIT could be a new therapeutic target in this special type of RCC. ..
- Subramanian S, West R, Corless C, Ou W, Rubin B, Chu K, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene. 2004;23:7780-90 pubmed..These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated. ..
- Blume Jensen P, Siegbahn A, Stabel S, Heldin C, Ronnstrand L. Increased Kit/SCF receptor induced mitogenicity but abolished cell motility after inhibition of protein kinase C. EMBO J. 1993;12:4199-209 pubmed..Our data suggest that PKC is involved in a negative feedback loop which regulates the Kit/SCF-R and that the activity of PKC determines whether the effect of SCF will be preferentially mitogenic or motogenic. ..
- Weiler S, Mou S, DeBerry C, Keller J, Ruscetti F, Ferris D, et al. JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor. Blood. 1996;87:3688-93 pubmed..These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway. ..
- Yavuz A, Lipsky P, Yavuz S, Metcalfe D, Akin C. Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene. Blood. 2002;100:661-5 pubmed....
- Heinrich M, Corless C, Duensing A, McGreevey L, Chen C, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708-10 pubmed..Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs. ..
- Sommer G, Agosti V, Ehlers I, Rossi F, Corbacioglu S, Farkas J, et al. Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proc Natl Acad Sci U S A. 2003;100:6706-11 pubmed..Importantly, these results demonstrate that constitutive Kit signaling is critical and sufficient for induction of GIST and hyperplasia of interstitial cells of Cajal. ..
- Kemmer K, Corless C, Fletcher J, McGreevey L, Haley A, Griffith D, et al. KIT mutations are common in testicular seminomas. Am J Pathol. 2004;164:305-13 pubmed..These findings suggest that activating KIT mutations may contribute to tumorigenesis in a subset of seminomas, but are not involved in NSGCT...
- Raspollini M, Amunni G, Villanucci A, Baroni G, Taddei A, Taddei G. c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study. Ann Oncol. 2004;15:594-7 pubmed....
- Kohl T, Schnittger S, Ellwart J, Hiddemann W, Spiekermann K. KIT exon 8 mutations associated with core-binding factor (CBF)-acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor. Blood. 2005;105:3319-21 pubmed..Our data show that KIT exon 8 mutations represent gain-of-function mutations and might represent a new molecular target for treatment of CBF leukemias. ..
- Masson K, Heiss E, Band H, Ronnstrand L. Direct binding of Cbl to Tyr568 and Tyr936 of the stem cell factor receptor/c-Kit is required for ligand-induced ubiquitination, internalization and degradation. Biochem J. 2006;399:59-67 pubmed..Taken together, our findings reveal novel insights into the mechanisms by which Cbl negatively regulates c-Kit-mediated signalling. ..
- Aichberger K, Gleixner K, Mirkina I, Cerny Reiterer S, Peter B, Ferenc V, et al. Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast cells: role of KIT D816V and effects of various targeted drugs. Blood. 2009;114:5342-51 pubmed publisher..Targeting of Bcl-2 family members by drugs promoting Bim (re)-expression, or by BH3-mimetics such as obatoclax, may be an attractive therapy concept in SM. ..