• external side of plasma membrane • membrane • integral to membrane
• protein amino acid dephosphorylation • signal transduction • transmembrane receptor protein tyrosine kinase signaling pathway • protein kinase cascade • response to radiation • peptidyl-tyrosine phosphorylation • cytokine and chemokine mediated signaling pathway • hemopoiesis • pigmentation during development
NM_000222 (mRNA) NP_000213 (protein)
NM_021099 (mRNA) NP_066922 (protein)
Chr 5: 75.86 - 75.94 Mb
CD117, also called KIT, is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types.
This gene encodes the human homolog of the proto-oncogene c-kit. C-kit was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. This protein is a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene.
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. Specifically hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of CD117. Common lymphoid progenitors (CLP) expresses low surface levels of CD117.
CD117 also identifies the earliest thymocyte progenitors in the thymus. Specifically early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit.
Additionally mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117.
CD117 is the receptor for the cytokine stem cell factor (SCF), also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF.
CD117 is a receptor tyrosine kinase type III. When this receptor binds to SCF it forms a dimer which activates signaling through second messengers. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation.
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. Currently, G-CSF is the main drug used for mobilization. G-CSF indirectly activates CD117. Direct CD117 agonists are currently being developed as mobilization agents.
Role in cancer
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 tumour type, most commonly occurring as a single gene amplicon. Mutations of CD117 have also been implicated in leukemia, a cancer of hematopoietic progenitors, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib, a CD117 inhibitor, is determined by the mutation status of CD117.
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