CD117

V-kit Hardi-Zakerman 4, homolog mačijeg sarkoma viralnog onkogena
PDB prikaz baziran na 1pkg​.
Dostupne strukture
1PKG​, 1T45​, 1T46​, 2E9W​, 2EC8​, 2VIF​, 3G0E​, 3G0F​
Identifikatori
Simboli	KIT; C-Kit; CD117; PBT; SCFR
Vanjski ID	OMIM: 164920 MGI: 96677 HomoloGene: 187 GeneCards: KIT Gene
EC broj	2.7.10.1
Ontologija gena Molekularna funkcija • vezivanje nukleotida • vezivanje proteaza • aktivnost proteinske tirozinske kinaze • aktivnost transmembranskog receptora proteinske tirozinske kinaze • aktivnost receptorskog signalnog proteina tirozinske kinaze • receptorska aktivnost • aktivnost faktora receptora stem ćelija • proteinsko vezivanje • ATP vezivanje • citokinsko vezivanje • aktivnost proteinske homodimerizacije • vezivanje metalnog jona Celularna komponenta • ekstracelularni prostor • nukleus • citoplazma • ćelijska membrana • spoljašnja strana ćelijske membrane • integralno sa membranom Biološki proces • aktivacija MAPK aktivnosti • diferencijacija mijeloidnih progenitornih ćelija • diferencijacija limfoidnih progenitornih ćelija • glikosfingolipidni metabolički proces • prenos signala • signalni put transmembranskog receptora proteinske tirozinske kinaze • kaskada intracelularne proteinske kinaze • spermatogeneza • razvoj spermatida • pozitivna regulacija ćelijske proliferacije • razvoj muških gonada • respons na radijaciju • pozitivna regulacija genske ekspresije • pozitivna regulacija fosfolipaze C • pozitivna regulacija kaskade fosfatidilinozitol 3-kinaze • peptidil-tirozinska fosforilacija • citokinom posredovani signalni put • održavanje matičnih ćelija • prenos signala fosforilacijom
Ortolozi
Vrsta	Čovek	Miš
Entrez	3815	16590
Ensembl	ENSG00000157404	ENSMUSG00000005672
UniProt	P10721	P05532
RefSeq (mRNA)	NM_000222.2	NM_001122733.1
RefSeq (protein)	NP_000213.1	NP_001116205.1
Lokacija (UCSC)	Chr 4: 55.52 - 55.61 Mb	Chr 5: 75.97 - 76.05 Mb
PubMed pretraga	[1]	[2]

Receptor faktora rasta mastocita/matičnih ćelija (engl. Mast/stem cell growth factor receptor - SCFR), takođe poznat kao proto-onkogen c-Kit ili tirozinska proteinska kinaza Kit ili CD117, je protein koji je kod ljudi kodiran KIT genom.^[1] Višestruke transkriptne varijante koje kodiraju različite izoforme ovog gena su poznate.^[2] KIT prvi opisao nemački biohemičar Aksel Ulrič 1987. kao ćelijski homolog mačijeg sarkomnog viralnog onkogena v-kit.^[3]

Interakcije

CD117 formira interakcije sa:

• APS,^[4]
• BCR,^[5]
• CD63,^[6]
• CD81,^[6]
• CD9,^[6]
• CRK,^[7][7]
• CRKL,^[8][9]
• DOK1,^[10]
• FES,^[11][11]
• GRB10,^[12]
• Grb2,^[13][14][15]
• KITLG,^[16][17]
• LNK,^[18]
• LYN,^[10][19]
• MATK,^[20][21]
• MPDZ,^[22]
• PIK3R1,^[8][13][23]
• PTPN11,^[24][25]
• PTPN6,^[25][26]
• STAT1,^[27]
• SOCS1,^[13]
• SOCS6,^[28]
• SRC,^[29] i
• TEC.^[30]
• Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third изд.). USA: Oxford University Press. ISBN 019850229X. 
• Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley-Interscience. ISBN 0471205036. 
• Branden C; Tooze J. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN 0-8153-2305-0. 
• Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems (Book 44 изд.). Wiley Classics Library. ISBN 0471303097. 
• William P. Jencks (1987). Catalysis in Chemistry and Enzymology. Dover Publications. ISBN 0486654605. 

Reference

1. Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F (1997). „Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes”. Genomics. 39 (2): 216—26. PMID 9027509. doi:10.1006/geno.1996.4482. 
2. „Entrez Gene: KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog”. 
3. Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A (1987). „Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand”. EMBO J. 6 (11): 3341—51. PMC 553789 . PMID 2448137. 
4. Wollberg P, Lennartsson J, Gottfridsson E, Yoshimura A, Rönnstrand L (2003). „The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit”. Biochem. J. 370 (Pt 3): 1033—8. PMC 1223215 . PMID 12444928. doi:10.1042/BJ20020716. 
5. Hallek M, Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb HJ, Druker B, Griffin JD, Emmerich B, Ullrich A (1996). „Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells”. Br. J. Haematol. 94 (1): 5—16. PMID 8757502. doi:10.1046/j.1365-2141.1996.6102053.x. 
6. Anzai N, Lee Y, Youn BS, Fukuda S, Kim YJ, Mantel C, Akashi M, Broxmeyer HE (2002). „C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors”. Blood. 99 (12): 4413—21. PMID 12036870. doi:10.1182/blood.V99.12.4413. 
7. Lennartsson J, Wernstedt C, Engström U, Hellman U, Rönnstrand L (2003). „Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk”. Exp. Cell Res. 288 (1): 110—8. PMID 12878163. doi:10.1016/S0014-4827(03)00206-4. 
8. van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M (2000). „Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells”. Blood. 96 (10): 3406—13. PMID 11071635. 
9. Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (1997). „Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)”. J. Biol. Chem. 272 (15): 10248—53. PMID 9092574. doi:10.1074/jbc.272.15.10248. 
10. Liang X, Wisniewski D, Strife A, Shivakrupa, Clarkson B, Resh MD (2002). „Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling”. J. Biol. Chem. 277 (16): 13732—8. PMID 11825908. doi:10.1074/jbc.M200277200. CS1 одржавање: Вишеструка имена: списак аутора (веза)
11. Voisset E, Lopez S, Chaix A, Vita M, George C, Dubreuil P, De Sepulveda P (2010). „FES kinase participates in KIT-ligand induced chemotaxis”. Biochem. Biophys. Res. Commun. 393 (1): 174—8. PMID 20117079. doi:10.1016/j.bbrc.2010.01.116. 
12. Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (2002). „Role for the adaptor protein Grb10 in the activation of Akt”. Mol. Cell. Biol. 22 (4): 979—91. PMC 134632 . PMID 11809791. doi:10.1128/MCB.22.4.979-991.2002. 
13. De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (1999). „Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation”. EMBO J. 18 (4): 904—15. PMC 1171183 . PMID 10022833. doi:10.1093/emboj/18.4.904. 
14. Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L (1999). „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. 341 ( Pt 1): 211—6. PMC 1220349 . PMID 10377264. doi:10.1042/0264-6021:3410211. 
15. Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (1996). „Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway”. J. Biol. Chem. 271 (21): 12129—32. PMID 8647802. doi:10.1074/jbc.271.21.12129. 
16. Lev S, Yarden Y, Givol D (1992). „A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses”. J. Biol. Chem. 267 (15): 10866—73. PMID 1375232. 
17. Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, Yarden Y (1993). „Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor”. J. Biol. Chem. 268 (6): 4399—406. PMID 7680037. 
18. Gueller S, Gery S, Nowak V, Liu L, Serve H, Koeffler HP (2008). „Adaptor protein Lnk associates with Tyr(568) in c-Kit”. Biochem. J. 415 (2): 241—5. PMID 18588518. doi:10.1042/BJ20080102. 
19. Linnekin D, DeBerry CS, Mou S (1997). „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. 272 (43): 27450—5. PMID 9341198. doi:10.1074/jbc.272.43.27450. 
20. Jhun BH, Rivnay B, Price D, Avraham H (1995). „The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit”. J. Biol. Chem. 270 (16): 9661—6. PMID 7536744. doi:10.1074/jbc.270.16.9661. 
21. Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H (1997). „Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes”. J. Biol. Chem. 272 (9): 5915—20. PMID 9038210. doi:10.1074/jbc.272.9.5915. 
22. Mancini A, Koch A, Stefan M, Niemann H, Tamura T (2000). „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. 482 (1-2): 54—8. PMID 11018522. doi:10.1016/S0014-5793(00)02036-6. 
23. Serve H, Hsu YC, Besmer P (1994). „Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells”. J. Biol. Chem. 269 (8): 6026—30. PMID 7509796. 
24. Tauchi T, Feng GS, Marshall MS, Shen R, Mantel C, Pawson T, Broxmeyer HE (1994). „The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells”. J. Biol. Chem. 269 (40): 25206—11. PMID 7523381. 
25. Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA (1998). „SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain”. Mol. Cell. Biol. 18 (4): 2089—99. PMC 121439 . PMID 9528781. 
26. Yi T, Ihle JN (1993). „Association of hematopoietic cell phosphatase with c-Kit after stimulation with c-Kit ligand”. Mol. Cell. Biol. 13 (6): 3350—8. PMC 359793 . PMID 7684496. 
27. Deberry C, Mou S, Linnekin D (1997). „Stat1 associates with c-kit and is activated in response to stem cell factor”. Biochem. J. 327 ( Pt 1): 73—80. PMC 1218765 . PMID 9355737. 
28. Bayle J, Letard S, Frank R, Dubreuil P, De Sepulveda P (2004). „Suppressor of cytokine signaling 6 associates with KIT and regulates KIT receptor signaling”. J. Biol. Chem. 279 (13): 12249—59. PMID 14707129. doi:10.1074/jbc.M313381200. 
29. Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rönnstrand L (1999). „Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction”. Oncogene. 18 (40): 5546—53. PMID 10523831. doi:10.1038/sj.onc.1202929. 
30. Tang B, Mano H, Yi T, Ihle JN (1994). „Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding”. Mol. Cell. Biol. 14 (12): 8432—7. PMC 359382 . PMID 7526158. 

Literatura

• Lennartsson J, Rönnstrand L (2006). „The stem cell factor receptor/c-Kit as a drug target in cancer”. Curr. Cancer Drug Targ. 6 (1): 65—75. PMID 16475976. doi:10.2174/156800906775471725. 
• Rönnstrand L (2004). „Signal transduction via the stem cell factor receptor/c-Kit”. Cell. Mol. Life Sci. 61 (19–20): 2535—2548. PMID 15526160. doi:10.1007/s00018-004-4189-6. 
• Linnekin D (2000). „Early signaling pathways activated by c-Kit in hematopoietic cells”. Int. J. Biochem. Cell Biol. 31 (10): 1053—74. PMID 10582339. doi:10.1016/S1357-2725(99)00078-3. 
• Canonico B, Felici C, Papa S (2001). „CD117”. J. Biol. Regul. Homeost. Agents. 15 (1): 90—4. PMID 11388751. 
• Gupta R, Bain BJ, Knight CL (2002). „Cytogenetic and molecular genetic abnormalities in systemic mastocytosis”. Acta Haematol. 107 (2): 123—8. PMID 11919394. doi:10.1159/000046642. 
• Valent P; Ghannadan M; Hauswirth AW; et al. (2003). „Signal transduction-associated and cell activation-linked antigens expressed in human mast cells”. Int. J. Hematol. 75 (4): 357—62. PMID 12041664. doi:10.1007/BF02982124. 
• Sandberg AA, Bridge JA (2002). „Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors. gastrointestinal stromal tumors”. Cancer Genet. Cytogenet. 135 (1): 1—22. PMID 12072198. doi:10.1016/S0165-4608(02)00546-0. 
• Kitamura Y, Hirotab S (2005). „Kit as a human oncogenic tyrosine kinase”. Cell. Mol. Life Sci. 61 (23): 2924—31. PMID 15583854. doi:10.1007/s00018-004-4273-y. 
• Larizza L, Magnani I, Beghini A (2005). „The Kasumi-1 cell line: a t(8;21)-kit mutant model for acute myeloid leukemia”. Leuk. Lymphoma. 46 (2): 247—55. PMID 15621809. doi:10.1080/10428190400007565. 
• Miettinen M, Lasota J (2006). „KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation”. Appl. Immunohistochem. Mol. Morphol. 13 (3): 205—20. PMID 16082245. 
• Lasota J, Miettinen M (2007). „KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)”. Semin Diagn Pathol. 23 (2): 91—102. PMID 17193822. doi:10.1053/j.semdp.2006.08.006. 
• Patnaik MM, Tefferi A, Pardanani A (2007). „Kit: molecule of interest for the diagnosis and treatment of mastocytosis and other neoplastic disorders”. Current cancer drug targets. 7 (5): 492—503. PMID 17691909. doi:10.2174/156800907781386614. 
• Giebel LB, Strunk KM, Holmes SA, Spritz RA (1992). „Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene”. Oncogene. 7 (11): 2207—17. PMID 1279499. 
• Spritz RA, Droetto S, Fukushima Y (1992). „Deletion of the KIT and PDGFRA genes in a patient with piebaldism”. Am. J. Med. Genet. 44 (4): 492—5. PMID 1279971. doi:10.1002/ajmg.1320440422. 
• Spritz RA, Giebel LB, Holmes SA (1992). „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. 50 (2): 261—9. PMC 1682440 . PMID 1370874. 
• Duronio V; Welham MJ; Abraham S; et al. (1992). „p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein”. Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1587—91. PMC 48497 . PMID 1371879. doi:10.1073/pnas.89.5.1587. 
• André C; Martin E; Cornu F; et al. (1992). „Genomic organization of the human c-kit gene: evolution of the receptor tyrosine kinase subclass III”. Oncogene. 7 (4): 685—91. PMID 1373482. 
• Lev S, Yarden Y, Givol D (1992). „A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses”. J. Biol. Chem. 267 (15): 10866—73. PMID 1375232. 
• Fleischman RA (1992). „Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene”. J. Clin. Invest. 89 (6): 1713—7. PMC 295855 . PMID 1376329. doi:10.1172/JCI115772. 
• Vandenbark GR; deCastro CM; Taylor H; et al. (1992). „Cloning and structural analysis of the human c-kit gene”. Oncogene. 7 (7): 1259—66. PMID 1377810. 
• Alai M; Mui AL; Cutler RL; et al. (1992). „Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells”. J. Biol. Chem. 267 (25): 18021—5. PMID 1381360. 
• Ashman LK; Cambareri AC; To LB; et al. (1991). „Expression of the YB5.B8 antigen (c-kit proto-oncogene product) in normal human bone marrow”. Blood. 78 (1): 30—7. PMID 1712644. 
• Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third изд.). USA: Oxford University Press. ISBN 019850229X. 
• Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley-Interscience. ISBN 0471205036. 
• Branden C; Tooze J. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN 0-8153-2305-0. 
• Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems (Book 44 изд.). Wiley Classics Library. ISBN 0471303097. 
• William P. Jencks (1987). Catalysis in Chemistry and Enzymology. Dover Publications. ISBN 0486654605. 

Vidi još

• Citokinski receptor

Spoljašnje veze

• Proto-Oncogene+Proteins+c-kit на US National Library of Medicine Medical Subject Headings (MeSH)
• C-kit receptor