CD117

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
Species	Human	Mouse
Entrez	3815	16590
Ensembl	ENSG00000157404	ENSMUSG00000005672
UniProt	P10721	P05532
RefSeq (mRNA)	NM_000222	NM_001122733
RefSeq (protein)	NP_000213	NP_001116205
Location (UCSC)	Chr 4: 54.66 – 54.74 Mb	Chr 5: 75.57 – 75.66 Mb
PubMed search	[1]	[2]

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. Multiple transcript variants encoding different isoforms have been found for this gene. KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.

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. 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. 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.

CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. 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. 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.

Interactions

CD117 has been shown to interact with:

• APS,
• BCR,
• CD63,
• CD81,
• CD9,
• CRK,
• CRKL,
• DOK1,
• FES,
• GRB10,
• Grb2,
• KITLG,
• LNK,
• LYN,
• MATK,
• MPDZ,
• PIK3R1,
• PTPN11,
• PTPN6,
• STAT1,
• SOCS1,
• SOCS6,
• SRC, and
• TEC.

See also

• Cytokine receptor
• List of genes mutated in pigmented cutaneous lesions

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