proto-oncogene protein c-Kit

WordNet

gear consisting of a set of articles or tools for a specified purpose (同)outfit
a case for containing a set of articles
young of any of various fur-bearing animals; "a fox kit"
the 3rd letter of the Roman alphabet (同)c
(music) the keynote of the scale of C major
a general-purpose programing language closely associated with the UNIX operating system
street names for ketamine (同)jet, super acid, special K, honey oil, green, cat valium, super C
the 11th letter of the Roman alphabet (同)k
goddess personifying earth; counterpart of Akkadian Aruru

PrepTutorEJDIC

〈C〉(特定の目的のための)用具(器具など)一式 / 〈C〉一式の用具を入れる箱(袋など) / 〈U〉《おもに英》(旅行者・水夫・兵士などの衣類など)身の回り品一式 / 〈C〉(全体を構成する)部品(材料)の一そろい
=kitten
carbonの化学記号
Kelvin / Kindergarten / (チェスの)King / kalium(ラテン語)(=potassium)の化学記号
case[s]

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/10 14:34:25」(JST)

wiki en

Mast/stem cell growth factor receptor (SCFR), also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a receptor tyrosine kinase protein that in humans is encoded by the KIT gene.^[1] Multiple transcript variants encoding different isoforms have been found for this gene.^[2]^[3] KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.^[4]

Cell surface marker

Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. CD117 is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. To be specific, hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of CD117. Common lymphoid progenitors (CLP) express low surface levels of CD117. CD117 also identifies the earliest thymocyte progenitors in the thymus. To be specific, early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It is also a marker for mouse prostate stem cells.^[5] In addition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117.

Function

CD117 is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer.^[6] CD117 is a receptor tyrosine kinase type III, which binds to stem cell factor (a substance that causes certain types of cells to grow), also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. Signalling through CD117 plays a role in cell survival, proliferation, and differentiation.

Mobilization

Hematopoietic progenitor cells are normally present in the blood at low levels. Mobilization is the process by which progenitors are made to migrate from the bone marrow into the bloodstream, thus increasing their numbers in the blood. Mobilization is used clinically as a source of hematopoietic stem cells for hematopoietic stem cell transplantation (HSCT). Signaling through CD117 has been implicated in mobilization. At the current time, G-CSF is the main drug used for mobilization. G-CSF indirectly activates CD117. Plerixafor (an antagonist of CXCR4-SDF1) in combination with G-CSF, is also being used for mobilization of hematopoietic progenitor cells. Direct CD117 agonists are currently being developed as mobilization agents.

Role in cancer

Activating mutations in this gene are associated with gastrointestinal stromal tumors, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivating mutations are associated with the genetic defect piebaldism.^[2]

CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer.^[7] Seminomas, a subtype of testicular germ cell tumors, frequently have activating mutations in exon 17 of CD117. In addition, the gene encoding CD117 is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon.^[8] Mutations of CD117 have also been implicated in leukemia, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib (trade name Gleevec), a CD117 inhibitor, is determined by the mutation status of CD117. When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemia), the receptor is not inhibited by imatinib. In those cases other inhibitors such as dasatinib and nilotinib can be used.

Diagnostic relevance

Antibodies to CD117 are widely used in immunohistochemistry to help distinguish particular types of tumour in histological tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for CD117, but negative for markers such as desmin and S-100, which are positive in smooth muscle and neural tumors, which have a similar appearance. In GISTs, CD117 staining is typically cytoplasmic, with stronger accentuation along the cell membranes. CD117 antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinomas.^[9]

Interactions

CD117 has been shown to interact with:

APS,^[10]
BCR,^[11]
CD63,^[12]
CD81,^[12]
CD9,^[12]
CRK,^[13]^[13]
CRKL,^[14]^[15]
DOK1,^[16]
FES,^[17]^[17]
GRB10,^[18]
Grb2,^[19]^[20]^[21]
KITLG,^[22]^[23]
LNK,^[24]
LYN,^[16]^[25]
MATK,^[26]^[27]
MPDZ,^[28]
PIK3R1,^[14]^[19]^[29]
PTPN11,^[30]^[31]
PTPN6,^[31]^[32]
STAT1,^[33]
SOCS1,^[19]
SOCS6,^[34]
SRC,^[35] and
TEC.^[36]

References

^ Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F (January 1997). "Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes". Genomics 39 (2): 216–26. doi:10.1006/geno.1996.4482. PMID 9027509.
^ ^a ^b "Entrez Gene: KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog".
^ National Cancer Institute Dictionary of Cancer Terms. c-kit. Accessed October 13, 2014.
^ Yarden Y, Kuang WJ, Yang-Feng T, Coussens L, Munemitsu S, Dull TJ, Chen E, Schlessinger J, Francke U, Ullrich A (November 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.
^ Leong KG, Wang BE, Johnson L, Gao WQ (October 2008). "Generation of a prostate from a single adult stem cell". Nature 456 (7223): 804–8. doi:10.1038/nature07427. PMID 18946470.
^ Edling CE, Hallberg B (2007). "c-Kit--a hematopoietic cell essential receptor tyrosine kinase". Int. J. Biochem. Cell Biol. 39 (11): 1995–8. doi:10.1016/j.biocel.2006.12.005. PMID 17350321.
^ Jean-Loup Huret. "KIT". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Retrieved 2008-03-01.
^ McIntyre A, Summersgill B, Grygalewicz B, Gillis AJ, Stoop J, van Gurp RJ, Dennis N, Fisher C, Huddart R, Cooper C, Clark J, Oosterhuis JW, Looijenga LH, Shipley J (2005). "Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults". Cancer Res. 65 (18): 8085–9. doi:10.1158/0008-5472.CAN-05-0471. PMID 16166280.
^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 149–151. ISBN 1-84110-100-1.
^ Wollberg P, Lennartsson J, Gottfridsson E, Yoshimura A, Rönnstrand L (March 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. doi:10.1042/BJ20020716. PMC 1223215. PMID 12444928.
^ Hallek M, Danhauser-Riedl S, Herbst R, Warmuth M, Winkler A, Kolb HJ, Druker B, Griffin JD, Emmerich B, Ullrich A (July 1996). "Interaction of the receptor tyrosine kinase p145c-kit with the p210bcr/abl kinase in myeloid cells". Br. J. Haematol. 94 (1): 5–16. doi:10.1046/j.1365-2141.1996.6102053.x. PMID 8757502.
^ ^a ^b ^c Anzai N, Lee Y, Youn BS, Fukuda S, Kim YJ, Mantel C, Akashi M, Broxmeyer HE (June 2002). "C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors". Blood 99 (12): 4413–21. doi:10.1182/blood.V99.12.4413. PMID 12036870.
^ ^a ^b Lennartsson J, Wernstedt C, Engström U, Hellman U, Rönnstrand L (August 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. doi:10.1016/S0014-4827(03)00206-4. PMID 12878163.
^ ^a ^b van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M (November 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.
^ Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (April 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. doi:10.1074/jbc.272.15.10248. PMID 9092574.
^ ^a ^b Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (April 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. doi:10.1074/jbc.M200277200. PMID 11825908.
^ ^a ^b Voisset E, Lopez S, Chaix A, Vita M, George C, Dubreuil P, De Sepulveda P (February 2010). "FES kinase participates in KIT-ligand induced chemotaxis". Biochem. Biophys. Res. Commun. 393 (1): 174–8. doi:10.1016/j.bbrc.2010.01.116. PMID 20117079.
^ Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (February 2002). "Role for the adaptor protein Grb10 in the activation of Akt". Mol. Cell. Biol. 22 (4): 979–91. doi:10.1128/MCB.22.4.979-991.2002. PMC 134632. PMID 11809791.
^ ^a ^b ^c De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". EMBO J. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833.
^ Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L (July 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 (1): 211–6. doi:10.1042/0264-6021:3410211. PMC 1220349. PMID 10377264.
^ Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (May 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. doi:10.1074/jbc.271.21.12129. PMID 8647802.
^ Lev S, Yarden Y, Givol D (May 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.
^ Blechman JM, Lev S, Brizzi MF, Leitner O, Pegoraro L, Givol D, Yarden Y (February 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.
^ Gueller S, Gery S, Nowak V, Liu L, Serve H, Koeffler HP (October 2008). "Adaptor protein Lnk associates with Tyr(568) in c-Kit". Biochem. J. 415 (2): 241–5. doi:10.1042/BJ20080102. PMID 18588518.
^ Linnekin D, DeBerry CS, Mou S (October 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. doi:10.1074/jbc.272.43.27450. PMID 9341198.
^ Jhun BH, Rivnay B, Price D, Avraham H (April 1995). "The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit". J. Biol. Chem. 270 (16): 9661–6. doi:10.1074/jbc.270.16.9661. PMID 7536744.
^ Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H (February 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. doi:10.1074/jbc.272.9.5915. PMID 9038210.
^ Mancini A, Koch A, Stefan M, Niemann H, Tamura T (September 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. doi:10.1016/S0014-5793(00)02036-6. PMID 11018522.
^ Serve H, Hsu YC, Besmer P (February 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.
^ Tauchi T, Feng GS, Marshall MS, Shen R, Mantel C, Pawson T, Broxmeyer HE (October 1994). "The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells". J. Biol. Chem. 269 (40): 25206–11. PMID 7523381.
^ ^a ^b Kozlowski M, Larose L, Lee F, Le DM, Rottapel R, Siminovitch KA (April 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.
^ Yi T, Ihle JN (June 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.
^ Deberry C, Mou S, Linnekin D (October 1997). "Stat1 associates with c-kit and is activated in response to stem cell factor". Biochem. J. 327 (1): 73–80. PMC 1218765. PMID 9355737.
^ Bayle J, Letard S, Frank R, Dubreuil P, De Sepulveda P (March 2004). "Suppressor of cytokine signaling 6 associates with KIT and regulates KIT receptor signaling". J. Biol. Chem. 279 (13): 12249–59. doi:10.1074/jbc.M313381200. PMID 14707129.
^ Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rönnstrand L (September 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. doi:10.1038/sj.onc.1202929. PMID 10523831.
^ Tang B, Mano H, Yi T, Ihle JN (December 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.

External links

Proto-Oncogene Proteins c-kit at the US National Library of Medicine Medical Subject Headings (MeSH)
C-kit receptor entry in the public domain NCI Dictionary of Cancer Terms

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Related Pictures

★リンクテーブル★

リンク元	「粘膜下腫瘍」「造血幹細胞因子」
拡張検索	「癌原遺伝子産物c-Kit」「proto-oncogene protein c-Kit」
関連記事	「C」「K」「kit」「Ki」「c」

「粘膜下腫瘍」

V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
	PDB rendering based on 1pkg.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1PKG, 1QZJ, 1QZK, 1R01, 1T45, 1T46, 2E9W, 2EC8, 2VIF, 3G0E, 3G0F, 4HVS, 4K94, 4K9E, 4PGZ, 4U0I
Identifiers
Symbols	KIT ; C-Kit; CD117; PBT; SCFR
External IDs	OMIM: 164920 MGI: 96677 HomoloGene: 187 ChEMBL: 1936 GeneCards: KIT Gene
EC number	2.7.10.1
Gene ontology
Molecular function	• protease binding; • protein tyrosine kinase activity; • transmembrane receptor protein tyrosine kinase activity; • receptor signaling protein tyrosine kinase activity; • stem cell factor receptor activity; • protein binding; • ATP binding; • cytokine binding; • protein homodimerization activity; • metal ion binding;
Cellular component	• acrosomal vesicle; • extracellular space; • plasma membrane; • cell-cell junction; • external side of plasma membrane; • cytoplasmic side of plasma membrane; • integral component of membrane; • mast cell granule;
Biological process	• activation of MAPK activity; • ovarian follicle development; • myeloid progenitor cell differentiation; • lymphoid progenitor cell differentiation; • immature B cell differentiation; • dendritic cell cytokine production; • mast cell chemotaxis; • glycosphingolipid metabolic process; • inflammatory response; • signal transduction; • epidermal growth factor receptor signaling pathway; • spermatogenesis; • spermatid development; • positive regulation of cell proliferation; • germ cell migration; • regulation of cell shape; • visual learning; • fibroblast growth factor receptor signaling pathway; • male gonad development; • positive regulation of phospholipase C activity; • positive regulation of phosphatidylinositol 3-kinase signaling; • peptidyl-tyrosine phosphorylation; • cytokine-mediated signaling pathway; • stem cell maintenance; • signal transduction by protein phosphorylation; • lamellipodium assembly; • hemopoiesis; • T cell differentiation; • erythrocyte differentiation; • melanocyte differentiation; • positive regulation of cell migration; • positive regulation of pseudopodium assembly; • actin cytoskeleton reorganization; • mast cell cytokine production; • somatic stem cell maintenance; • embryonic hemopoiesis; • ectopic germ cell programmed cell death; • megakaryocyte development; • Fc receptor signaling pathway; • Fc-epsilon receptor signaling pathway; • Kit signaling pathway; • erythropoietin-mediated signaling pathway; • regulation of cell proliferation; • positive regulation of tyrosine phosphorylation of Stat1 protein; • positive regulation of tyrosine phosphorylation of Stat3 protein; • positive regulation of tyrosine phosphorylation of Stat5 protein; • negative regulation of programmed cell death; • mast cell degranulation; • positive regulation of MAPK cascade; • pigmentation; • positive regulation of phosphatidylinositol 3-kinase activity; • innate immune response; • positive regulation of Notch signaling pathway; • positive regulation of JAK-STAT cascade; • protein autophosphorylation; • neurotrophin TRK receptor signaling pathway; • phosphatidylinositol-mediated signaling; • regulation of developmental pigmentation; • somatic stem cell division; • positive regulation of long-term neuronal synaptic plasticity; • digestive tract development; • stem cell differentiation; • epithelial cell proliferation; • detection of mechanical stimulus involved in sensory perception of sound; • positive regulation of sequence-specific DNA binding transcription factor activity; • cell chemotaxis; • mast cell differentiation; • mast cell proliferation; • cellular response to thyroid hormone stimulus; • melanocyte migration; • melanocyte adhesion;
	Sources: Amigo / QuickGO
Orthologs
	v; t; e;