Mast/stem cell growth factor receptor Kit

Details

Name
Mast/stem cell growth factor receptor Kit
Synonyms
  • 2.7.10.1
  • p145 c-kit
  • PBT
  • Piebald trait protein
  • Proto-oncogene c-Kit
  • SCFR
  • Tyrosine-protein kinase Kit
  • v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
Gene Name
KIT
UniProtKB Entry
P10721Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000903|Mast/stem cell growth factor receptor Kit
MRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTD
PGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLV
DRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYH
RLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSS
SVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSAN
VTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWE
DYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDR
LVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDS
SAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIV
MILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAF
GKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGAC
TIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE
YMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGM
AFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPES
IFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMY
DIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSV
GSTASSSQPLLVHDDV
Number of residues
976
Molecular Weight
109863.655
Theoretical pI
6.96
GO Classification
Functions
growth factor binding / protease binding / SH2 domain binding
Processes
actin cytoskeleton organization / B cell differentiation / hematopoietic progenitor cell differentiation / hematopoietic stem cell migration / intracellular signal transduction / negative regulation of developmental process / negative regulation of reproductive process / positive regulation of colon smooth muscle contraction / positive regulation of dendritic cell cytokine production / positive regulation of DNA-binding transcription factor activity / positive regulation of mast cell cytokine production / positive regulation of mast cell proliferation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of pyloric antrum smooth muscle contraction / positive regulation of receptor signaling pathway via JAK-STAT / positive regulation of small intestine smooth muscle contraction / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell differentiation / regulation of bile acid metabolic process / regulation of cell population proliferation / response to cadmium ion / tongue development
Components
fibrillar center / receptor complex
General Function
Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1
Specific Function
Atp binding
Pfam Domain Function
Signal Regions
1-25
Transmembrane Regions
525-545
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020461|Mast/stem cell growth factor receptor Kit (KIT)
ATGAGAGGCGCTCGCGGCGCCTGGGATTTTCTCTGCGTTCTGCTCCTACTGCTTCGCGTC
CAGACAGGCTCTTCTCAACCATCTGTGAGTCCAGGGGAACCGTCTCCACCATCCATCCAT
CCAGGAAAATCAGACTTAATAGTCCGCGTGGGCGACGAGATTAGGCTGTTATGCACTGAT
CCGGGCTTTGTCAAATGGACTTTTGAGATCCTGGATGAAACGAATGAGAATAAGCAGAAT
GAATGGATCACGGAAAAGGCAGAAGCCACCAACACCGGCAAATACACGTGCACCAACAAA
CACGGCTTAAGCAATTCCATTTATGTGTTTGTTAGAGATCCTGCCAAGCTTTTCCTTGTT
GACCGCTCCTTGTATGGGAAAGAAGACAACGACACGCTGGTCCGCTGTCCTCTCACAGAC
CCAGAAGTGACCAATTATTCCCTCAAGGGGTGCCAGGGGAAGCCTCTTCCCAAGGACTTG
AGGTTTATTCCTGACCCCAAGGCGGGCATCATGATCAAAAGTGTGAAACGCGCCTACCAT
CGGCTCTGTCTGCATTGTTCTGTGGACCAGGAGGGCAAGTCAGTGCTGTCGGAAAAATTC
ATCCTGAAAGTGAGGCCAGCCTTCAAAGCTGTGCCTGTTGTGTCTGTGTCCAAAGCAAGC
TATCTTCTTAGGGAAGGGGAAGAATTCACAGTGACGTGCACAATAAAAGATGTGTCTAGT
TCTGTGTACTCAACGTGGAAAAGAGAAAACAGTCAGACTAAACTACAGGAGAAATATAAT
AGCTGGCATCACGGTGACTTCAATTATGAACGTCAGGCAACGTTGACTATCAGTTCAGCG
AGAGTTAATGATTCTGGAGTGTTCATGTGTTATGCCAATAATACTTTTGGATCAGCAAAT
GTCACAACAACCTTGGAAGTAGTAGATAAAGGATTCATTAATATCTTCCCCATGATAAAC
ACTACAGTATTTGTAAACGATGGAGAAAATGTAGATTTGATTGTTGAATATGAAGCATTC
CCCAAACCTGAACACCAGCAGTGGATCTATATGAACAGAACCTTCACTGATAAATGGGAA
GATTATCCCAAGTCTGAGAATGAAAGTAATATCAGATACGTAAGTGAACTTCATCTAACG
AGATTAAAAGGCACCGAAGGAGGCACTTACACATTCCTAGTGTCCAATTCTGACGTCAAT
GCTGCCATAGCATTTAATGTTTATGTGAATACAAAACCAGAAATCCTGACTTACGACAGG
CTCGTGAATGGCATGCTCCAATGTGTGGCAGCAGGATTCCCAGAGCCCACAATAGATTGG
TATTTTTGTCCAGGAACTGAGCAGAGATGCTCTGCTTCTGTACTGCCAGTGGATGTGCAG
ACACTAAACTCATCTGGGCCACCGTTTGGAAAGCTAGTGGTTCAGAGTTCTATAGATTCT
AGTGCATTCAAGCACAATGGCACGGTTGAATGTAAGGCTTACAACGATGTGGGCAAGACT
TCTGCCTATTTTAACTTTGCATTTAAAGGTAACAACAAAGAGCAAATCCATCCCCACACC
CTGTTCACTCCTTTGCTGATTGGTTTCGTAATCGTAGCTGGCATGATGTGCATTATTGTG
ATGATTCTGACCTACAAATATTTACAGAAACCCATGTATGAAGTACAGTGGAAGGTTGTT
GAGGAGATAAATGGAAACAATTATGTTTACATAGACCCAACACAACTTCCTTATGATCAC
AAATGGGAGTTTCCCAGAAACAGGCTGAGTTTTGGGAAAACCCTGGGTGCTGGAGCTTTC
GGGAAGGTTGTTGAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGACTGTC
GCTGTAAAGATGCTCAAGCCGAGTGCCCATTTGACAGAACGGGAAGCCCTCATGTCTGAA
CTCAAAGTCCTGAGTTACCTTGGTAATCACATGAATATTGTGAATCTACTTGGAGCCTGC
ACCATTGGAGGGCCCACCCTGGTCATTACAGAATATTGTTGCTATGGTGATCTTTTGAAT
TTTTTGAGAAGAAAACGTGATTCATTTATTTGTTCAAAGCAGGAAGATCATGCAGAAGCT
GCACTTTATAAGAATCTTCTGCATTCAAAGGAGTCTTCCTGCAGCGATAGTACTAATGAG
TACATGGACATGAAACCTGGAGTTTCTTATGTTGTCCCAACCAAGGCCGACAAAAGGAGA
TCTGTGAGAATAGGCTCATACATAGAAAGAGATGTGACTCCCGCCATCATGGAGGATGAC
GAGTTGGCCCTAGACTTAGAAGACTTGCTGAGCTTTTCTTACCAGGTGGCAAAGGGCATG
GCTTTCCTCGCCTCCAAGAATTGTATTCACAGAGACTTGGCAGCCAGAAATATCCTCCTT
ACTCATGGTCGGATCACAAAGATTTGTGATTTTGGTCTAGCCAGAGACATCAAGAATGAT
TCTAATTATGTGGTTAAAGGAAACGCTCGACTACCTGTGAAGTGGATGGCACCTGAAAGC
ATTTTCAACTGTGTATACACGTTTGAAAGTGACGTCTGGTCCTATGGGATTTTTCTTTGG
GAGCTGTTCTCTTTAGGAAGCAGCCCCTATCCTGGAATGCCGGTCGATTCTAAGTTCTAC
AAGATGATCAAGGAAGGCTTCCGGATGCTCAGCCCTGAACACGCACCTGCTGAAATGTAT
GACATAATGAAGACTTGCTGGGATGCAGATCCCCTAAAAAGACCAACATTCAAGCAAATT
GTTCAGCTAATTGAGAAGCAGATTTCAGAGAGCACCAATCATATTTACTCCAACTTAGCA
AACTGCAGCCCCAACCGACAGAAGCCCGTGGTAGACCATTCTGTGCGGATCAATTCTGTC
GGCAGCACCGCTTCCTCCTCCCAGCCTCTGCTTGTGCACGACGATGTCTGA
Chromosome Location
4
Locus
4q12
External Identifiers
ResourceLink
UniProtKB IDP10721
UniProtKB Entry NameKIT_HUMAN
GenBank Protein ID34085
GenBank Gene IDX06182
GeneCard IDKIT
GenAtlas IDKIT
HGNC IDHGNC:6342
PDB ID(s)1PKG, 1T45, 1T46, 2E9W, 2EC8, 2IUH, 2VIF, 3G0E, 3G0F, 4HVS, 4K94, 4K9E, 4PGZ, 4U0I, 6GQJ, 6GQK, 6GQL, 6GQM, 6HH1, 6ITT, 6ITV, 6KLA, 6MOB, 6XV9, 6XVA, 6XVB, 7KHG, 7KHJ, 7KHK, 7ZW8, 7ZY6, 8DFM, 8DFP, 8DFQ, 8PQ9, 8PQA, 8PQB, 8PQC, 8PQD, 8PQE, 8PQF, 8PQG
KEGG IDhsa:3815
IUPHAR/Guide To Pharmacology ID1805
NCBI Gene ID3815
General References
  1. Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A: Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341-51. [Article]
  2. Giebel LB, Strunk KM, Holmes SA, Spritz RA: Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. Oncogene. 1992 Nov;7(11):2207-17. [Article]
  3. Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F: Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes. Genomics. 1997 Jan 15;39(2):216-26. [Article]
  4. Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM: Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther. 2008;10(4):R73. doi: 10.1186/ar2447. Epub 2008 Jul 1. [Article]
  5. Neumann I, Foell JL, Bremer M, Volkmer I, Korholz D, Burdach S, Staege MS: Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate. Pediatr Blood Cancer. 2010 Sep;55(3):464-70. doi: 10.1002/pbc.22603. [Article]
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  7. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  9. Yamamoto K, Tojo A, Aoki N, Shibuya M: Characterization of the promoter region of the human c-kit proto-oncogene. Jpn J Cancer Res. 1993 Nov;84(11):1136-44. [Article]
  10. Blume-Jensen P, Ronnstrand L, Gout I, Waterfield MD, Heldin CH: Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase C. J Biol Chem. 1994 Aug 26;269(34):21793-802. [Article]
  11. Blume-Jensen P, Wernstedt C, Heldin CH, Ronnstrand L: Identification of the major phosphorylation sites for protein kinase C in kit/stem cell factor receptor in vitro and in intact cells. J Biol Chem. 1995 Jun 9;270(23):14192-200. [Article]
  12. Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H: Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes. J Biol Chem. 1997 Feb 28;272(9):5915-20. [Article]
  13. Linnekin D, DeBerry CS, Mou S: Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells. J Biol Chem. 1997 Oct 24;272(43):27450-5. [Article]
  14. Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA: SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain. Mol Cell Biol. 1998 Apr;18(4):2089-99. [Article]
  15. Thommes K, Lennartsson J, Carlberg M, Ronnstrand L: Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor. Biochem J. 1999 Jul 1;341 ( Pt 1):211-6. [Article]
  16. Taniguchi Y, London R, Schinkmann K, Jiang S, Avraham H: The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and Is associated with the c-Kit receptor. Blood. 1999 Jul 15;94(2):539-49. [Article]
  17. Mancini A, Koch A, Stefan M, Niemann H, Tamura T: The direct association of the multiple PDZ domain containing proteins (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase activity. FEBS Lett. 2000 Sep 29;482(1-2):54-8. [Article]
  18. Liang X, Wisniewski D, Strife A, Shivakrupa, Clarkson B, Resh MD: Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling. J Biol Chem. 2002 Apr 19;277(16):13732-8. Epub 2002 Feb 1. [Article]
  19. Wollberg P, Lennartsson J, Gottfridsson E, Yoshimura A, Ronnstrand L: The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit. Biochem J. 2003 Mar 15;370(Pt 3):1033-8. [Article]
  20. Lennartsson J, Wernstedt C, Engstrom U, Hellman U, Ronnstrand L: Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk. Exp Cell Res. 2003 Aug 1;288(1):110-8. [Article]
  21. Voytyuk O, Lennartsson J, Mogi A, Caruana G, Courtneidge S, Ashman LK, Ronnstrand L: Src family kinases are involved in the differential signaling from two splice forms of c-Kit. J Biol Chem. 2003 Mar 14;278(11):9159-66. Epub 2003 Jan 2. [Article]
  22. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [Article]
  23. Voisset E, Lopez S, Dubreuil P, De Sepulveda P: The tyrosine kinase FES is an essential effector of KITD816V proliferation signal. Blood. 2007 Oct 1;110(7):2593-9. Epub 2007 Jun 26. [Article]
  24. Sun J, Pedersen M, Bengtsson S, Ronnstrand L: Grb2 mediates negative regulation of stem cell factor receptor/c-Kit signaling by recruitment of Cbl. Exp Cell Res. 2007 Nov 1;313(18):3935-42. Epub 2007 Sep 4. [Article]
  25. Sun J, Pedersen M, Ronnstrand L: The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction. J Biol Chem. 2009 Apr 24;284(17):11039-47. doi: 10.1074/jbc.M808058200. Epub 2009 Mar 5. [Article]
  26. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  27. Muciaccia B, Sette C, Paronetto MP, Barchi M, Pensini S, D'Agostino A, Gandini L, Geremia R, Stefanini M, Rossi P: Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity. Hum Reprod. 2010 Sep;25(9):2188-202. doi: 10.1093/humrep/deq168. Epub 2010 Jul 3. [Article]
  28. DiNitto JP, Deshmukh GD, Zhang Y, Jacques SL, Coli R, Worrall JW, Diehl W, English JM, Wu JC: Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance. J Biochem. 2010 Apr;147(4):601-9. doi: 10.1093/jb/mvq015. Epub 2010 Feb 10. [Article]
  29. Kim SY, Kang JJ, Lee HH, Kang JJ, Kim B, Kim CG, Park TK, Kang H: Mechanism of activation of human c-KIT kinase by internal tandem duplications of the juxtamembrane domain and point mutations at aspartic acid 816. Biochem Biophys Res Commun. 2011 Jul 1;410(2):224-8. doi: 10.1016/j.bbrc.2011.05.111. Epub 2011 May 27. [Article]
  30. Chaix A, Lopez S, Voisset E, Gros L, Dubreuil P, De Sepulveda P: Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells. J Biol Chem. 2011 Feb 25;286(8):5956-66. doi: 10.1074/jbc.M110.182642. Epub 2010 Dec 6. [Article]
  31. Ronnstrand L: Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48. doi: 10.1007/s00018-004-4189-6. [Article]
  32. Roskoski R Jr: Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor. Biochem Biophys Res Commun. 2005 Nov 11;337(1):1-13. [Article]
  33. Lennartsson J, Jelacic T, Linnekin D, Shivakrupa R: Normal and oncogenic forms of the receptor tyrosine kinase kit. Stem Cells. 2005;23(1):16-43. [Article]
  34. Kent D, Copley M, Benz C, Dykstra B, Bowie M, Eaves C: Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway. Clin Cancer Res. 2008 Apr 1;14(7):1926-30. doi: 10.1158/1078-0432.CCR-07-5134. [Article]
  35. Pittoni P, Piconese S, Tripodo C, Colombo MP: Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors. Oncogene. 2011 Feb 17;30(7):757-69. doi: 10.1038/onc.2010.494. Epub 2010 Nov 8. [Article]
  36. Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE: Structure of a c-kit product complex reveals the basis for kinase transactivation. J Biol Chem. 2003 Aug 22;278(34):31461-4. Epub 2003 Jun 24. [Article]
  37. Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, Snell GP, Zou H, Sang BC, Wilson KP: Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004 Jul 23;279(30):31655-63. Epub 2004 Apr 29. [Article]
  38. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J: Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007 Jul 27;130(2):323-34. [Article]
  39. Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, English JM, Greig MJ, He YA, Jacques SL, Lunney EA, McTigue M, Molina D, Quenzer T, Wells PA, Yu X, Zhang Y, Zou A, Emmett MR, Marshall AG, Zhang HM, Demetri GD: KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1542-7. doi: 10.1073/pnas.0812413106. Epub 2009 Jan 21. [Article]
  40. Zadjali F, Pike AC, Vesterlund M, Sun J, Wu C, Li SS, Ronnstrand L, Knapp S, Bullock AN, Flores-Morales A: Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. J Biol Chem. 2011 Jan 7;286(1):480-90. doi: 10.1074/jbc.M110.173526. Epub 2010 Oct 28. [Article]
  41. Fleischman RA: Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene. J Clin Invest. 1992 Jun;89(6):1713-7. [Article]
  42. Spritz RA, Giebel LB, Holmes SA: Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. Am J Hum Genet. 1992 Feb;50(2):261-9. [Article]
  43. Giebel LB, Spritz RA: Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8696-9. [Article]
  44. Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, Sugahara H, Butterfield JH, Ashman LK, Kanayama Y, 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 Oct;92(4):1736-44. [Article]
  45. Spritz RA, Holmes SA, Itin P, Kuster W: Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. J Invest Dermatol. 1993 Jul;101(1):22-5. [Article]
  46. Riva P, Milani N, Gandolfi P, Larizza L: A 12-bp deletion (7818del12) in the c-kit protooncogene in a large Italian kindred with piebaldism. Hum Mutat. 1995;6(4):343-5. [Article]
  47. Pignon JM, Giraudier S, Duquesnoy P, Jouault H, Imbert M, Vainchenker W, Vernant JP, Tulliez M: A new c-kit mutation in a case of aggressive mast cell disease. Br J Haematol. 1997 Feb;96(2):374-6. [Article]
  48. Spritz RA, Beighton P: Piebaldism with deafness: molecular evidence for an expanded syndrome. Am J Med Genet. 1998 Jan 6;75(1):101-3. [Article]
  49. Beghini A, Larizza L, Cairoli R, Morra E: c-kit activating mutations and mast cell proliferation in human leukemia. Blood. 1998 Jul 15;92(2):701-2. [Article]
  50. Nomura K, Hatayama I, Narita T, Kaneko T, Shiraishi M: A novel KIT gene missense mutation in a Japanese family with piebaldism. J Invest Dermatol. 1998 Aug;111(2):337-8. [Article]
  51. Nishida T, Hirota S, Taniguchi M, Hashimoto K, Isozaki K, Nakamura H, Kanakura Y, Tanaka T, Takabayashi A, Matsuda H, Kitamura Y: Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet. 1998 Aug;19(4):323-4. [Article]
  52. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998 Jan 23;279(5350):577-80. [Article]
  53. Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA: Activating c-kit gene mutations in human germ cell tumors. Am J Pathol. 1999 Jun;154(6):1643-7. [Article]
  54. Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y: Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1609-14. [Article]
  55. Syrris P, Malik NM, Murday VA, Patton MA, Carter ND, Hughes HE, Metcalfe K: Three novel mutations of the proto-oncogene KIT cause human piebaldism. Am J Med Genet. 2000 Nov 6;95(1):79-81. [Article]
  56. Beghini A, Tibiletti MG, Roversi G, Chiaravalli AM, Serio G, Capella C, Larizza L: Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa. Cancer. 2001 Aug 1;92(3):657-62. [Article]
  57. Chen LL, Sabripour M, Wu EF, Prieto VG, Fuller GN, Frazier ML: A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors. Oncogene. 2005 Jun 16;24(26):4271-80. [Article]
  58. Bignell G, Smith R, Hunter C, Stephens P, Davies H, Greenman C, Teague J, Butler A, Edkins S, Stevens C, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Gillis AJ, Stoop HJ, van Gurp RJ, Oosterhuis JW, Looijenga LH, Futreal PA, Wooster R, Stratton MR: Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Genes Chromosomes Cancer. 2006 Jan;45(1):42-6. [Article]
  59. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Mast/stem cell growth factor receptor Kit (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Sorafenibapproved, investigationalyestargetantagonistDetails
ImatinibapprovedyestargetantagonistDetails
Dasatinibapproved, investigationalyestargetantagonistDetails
Sunitinibapproved, investigationalyestargetinhibitorDetails
PhosphonotyrosineexperimentalyestargetinhibitorDetails
Nilotinibapproved, investigationalunknowntargetantagonistDetails
AmuvatinibinvestigationalyestargetmodulatorDetails
XL820investigationalunknowntargetDetails
LinifanibinvestigationalunknowntargetDetails
OSI-930investigationalyestargetmodulatorDetails
PazopanibapprovedyestargetinhibitorDetails
Midostaurinapproved, investigationalunknowntargetantagonistinhibitorDetails
RegorafenibapprovedyestargetinhibitorDetails
Ponatinibapproved, investigationalunknowntargetinhibitorDetails
Lenvatinibapproved, investigationalyestargetinhibitorDetails
Ancestimapproved, investigational, withdrawnyestargetagonistDetails
Fostamatinibapproved, investigationalunknowntargetinhibitorDetails
Erdafitinibapproved, investigationalunknowntargetsubstrateDetails
Pexidartinibapproved, investigationalyestargetinhibitorDetails
Avapritinibapproved, investigationalunknowntargetinhibitorDetails
RipretinibapprovedyestargetinhibitorDetails
Tivozanibapproved, investigationalyestargetinhibitorDetails
JNJ-28312141investigationalyestargetinhibitorDetails
PD-166326experimentalyestargetinhibitorDetails
MotesanibinvestigationalyestargetinhibitorDetails
FamitinibinvestigationalyestargetinhibitorDetails
SemaxanibinvestigationalyestargetinhibitorDetails
BezuclastinibinvestigationalyestargetinhibitorDetails