CD117

  • OMIM: 164920
  • UniProt: P10721
  • MGI: 96677

KIT tyrosine kinase (also: CD117, c- kit and stem cell factor receptor ) is a cell membrane of various cells of the body occurring protein belonging to the family of receptor tyrosine kinases. This protein is the gene product of the protooncogene c-kit, i.e. a precursor of a potentially cancer-causing gene product, and was discovered in 1987 by Ullrich et al as a homologue of the viral oncogene v - kit.

Function

C-Kit is particularly formed in hematopoietic stem cells, but also comes in a number of other cell lines, such as multipotent ( MPPs ) and myeloid progenitor cells ( CMPs ) ago. As a receptor protein can c-Kit by its ligand, the stem cell factor (SCF ), are activated. c- kit plays an important role in the proliferation and differentiation of stem cells and is therefore of great importance for angiogenesis and hematopoiesis, and plays an important role in the pigmentation of the skin, bowel function and spermatogenesis.

Mutations permanently activated c-Kit plays a role in several forms of cancer, in particular germ cell tumors, melanoma, leukemia, mastocytosis, and mast cell tumors. These cancers tyrosine kinase inhibitors can be used. c-Kit inactivating mutations in homozygous carriers usually to death already in the embryonic or can cause fertility problems in heterozygotes, leucism and piebald.

Even in insects plays c- kit in spermatogenesis a role.

Biochemistry

Structure

C- kit is a cell membrane by the spanning protein ( transmembrane protein) having a molecular weight of about 110 kDa, which is encoded by a gene on chromosome 4 q11 - q12 locus. Its extracellular part consists of five immunoglobulin -like domains, which are involved in the binding of its ligand, stem cell factor. As related receptor tyrosine kinases consists of the transmembrane part of c- kit consists of a single helix. The intracellular portion of c- kit kinase domain carries a two-part, which is responsible for signal transduction.

Activation

As is typical of many receptor tyrosine kinases induces even in the case of c- kit, a connection of its ligand in the dimeric form of receptor dimerization. c-Kit has an intrinsic kinase function and as a result of dimerization of c- kit autophosphorylation can be observed by cross- phosphorylation of tyrosine groups of the intracellular domains. Phosphorylated and thus activated receptor serves as a binding site for another signal transduction, which have a Phosphotyrosinbindungsstelle or SH2 domain. These include the kinases of the Src family, the Janus kinase JAK2 and phosphoinositide 3 - kinases, which in turn can activate a variety of signal transduction pathways.

Further Reading

  • Lennartsson J., T. Jelacic, D. Linnekin, Shivakrupa R. ( 2005). Normal and oncogenic forms of the receptor tyrosine kinase kit. Stem Cells 23:16-43.

Swell

  • Protein kinase
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