CD117

Mast/stem cell growth factor receptor (SCFR), also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a is_associated_with::receptor tyrosine kinase is_associated_with::protein that in humans is encoded by the KIT is_associated_with::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
is_associated_with::Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of is_associated_with::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 is_associated_with::hematopoietic (blood) progenitors in the is_associated_with::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 is_associated_with::thymocyte progenitors in the is_associated_with::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 is_associated_with::prostate is_associated_with::stem cells. In addition, is_associated_with::mast cells, is_associated_with::melanocytes in the skin, and is_associated_with::interstitial cells of Cajal in the is_associated_with::digestive tract express CD117.

Function
CD117 is a is_associated_with::cytokine receptor expressed on the surface of is_associated_with::hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of is_associated_with::cancer. CD117 is a is_associated_with::receptor tyrosine kinase type III, which binds to is_associated_with::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 is_associated_with::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 is_associated_with::hematopoietic stem cell transplantation (HSCT). Signaling through CD117 has been implicated in mobilization. At the current time, is_associated_with::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 is_associated_with::agonists are currently being developed as mobilization agents.

Role in cancer
Activating mutations in this gene are associated with is_associated_with::gastrointestinal stromal tumors, testicular is_associated_with::seminoma, mast cell disease, is_associated_with::melanoma, is_associated_with::acute myeloid leukemia, while inactivating mutations are associated with the genetic defect is_associated_with::piebaldism.

CD117 is a is_associated_with::proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. Seminomas, a subtype of testicular is_associated_with::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 is_associated_with::leukemia, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and is_associated_with::gastrointestinal stromal tumors (GISTs). The efficacy of is_associated_with::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 is_associated_with::imatinib. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemia), the receptor is not inhibited by is_associated_with::imatinib. In those cases other inhibitors such as is_associated_with::dasatinib and is_associated_with::nilotinib can be used.

Diagnostic relevance
Antibodies to CD117 are widely used in is_associated_with::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 is_associated_with::desmin and S-100, which are positive in smooth muscle and neural tumors, which have a similar appearance. In GISTs, CD117 staining is typically is_associated_with::cytoplasmic, with stronger accentuation along the is_associated_with::cell membranes. CD117 antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing is_associated_with::seminomas from is_associated_with::embryonal carcinomas.

Interactions
CD117 has been shown to interact with:


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