Tyrosine Kinase KIT
| Tyrosine Kinase KIT | ||
|---|---|---|
|
||
| Surface model of the interaction of c-Kit (gray) with its ligand (green) according to PDB 2E9W | ||
| Mass / length primary structure | 976 amino acids | |
| Secondary to quaternary structure | Homodimer | |
| Identifier | ||
| Gene name (s) | KIT; c-kit; CD117; SCFR | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 2.7.10.1 , tyrosine kinase | |
| Response type | Autophosphorylation | |
| Occurrence | ||
| Parent taxon | Bilateria | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 3815 | 16590 |
| Ensemble | ENSG00000157404 | ENSMUSG00000005672 |
| UniProt | P10721 | P05532 |
| Refseq (mRNA) | NM_000222 | NM_001122733 |
| Refseq (protein) | NP_000213 | NP_001116205 |
| Gene locus | Chr 4: 54.66 - 54.74 Mb | Chr 5: 75.57 - 75.66 Mb |
| PubMed search | 3815 |
16590
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The tyrosine kinase KIT (also: CD117 , c-Kit or stem cell factor receptor ) is a protein from the family of receptor tyrosine kinases that occurs in the cell membrane of various body cells . This protein is the gene product of the proto-oncogene c-kit , i. H. a potentially cancer-causing gene and was discovered in 1987 by Axel Ullrich and co-workers as a homolog of the viral oncogene v-Kit .
function
c-Kit is formed in particular in hematopoietic stem cells , but is also found in a number of other cell lines , such as multipotent (MPPs) and myeloid progenitor cells (CMPs). As a receptor protein , c-Kit can be activated by its ligand , the stem cell factor (SCF). c-Kit plays a crucial role in the proliferation and differentiation of stem cells and is therefore of great importance for hematopoiesis and angiogenesis and plays an important role in skin pigmentation , intestinal function and spermatogenesis .
C-Kit, which is permanently activated by mutations, plays a role in various forms of cancer, in particular germ cell tumors , melanomas , leukemias , mastocytoses and mast cell tumors . Tyrosine kinase inhibitors can be used in these cancers . Mutations that inactivate c-Kit lead to death in homozygous carriers as a rule in the embryonic phase or can cause fertility disorders , leucism and spotting in heterozygous persons .
The c-Kit also plays a role in spermatogenesis in insects.
biochemistry
structure
c-Kit is a protein that spans the cell membrane ( transmembrane protein ) with a molar mass of about 110 kDa , which is encoded by a gene on chromosome 4 gene locus q11-q12. Its extracellular part consists of 5 immunoglobulin-like domains that are involved in the binding of its ligand, the stem cell factor. Like related receptor tyrosine kinases, the transmembrane portion of c-Kit consists of a single helix . The intracellular part of c-Kit carries a two-part kinase domain that is responsible for signal transduction .
activation
As is typical for many receptor tyrosine kinases, binding of its ligand in dimeric form also induces dimerization of the receptor in the case of c-Kit . c-Kit has an intrinsic kinase function and, as a result of the dimerization of c-Kit, autophosphorylation by mutual phosphorylation of tyrosine groups of the intracellular domains can be observed. The phosphorylated and thus activated receptor serves as a binding site for further signal transduction molecules that have a phosphotyrosine binding site or an SH2 domain . These include, for example, the kinases of the Src family , the Janus kinase JAK2 and the phosphoinositide-3-kinases , which in turn can activate a large number of signal transduction pathways.
further reading
- J. Lennartsson, T. Jelacic, D. Linnekin, R. Shivakrupa: Normal and oncogenic forms of the receptor tyrosine kinase kit. In: Stem Cells . 23, 2005, pp. 16-43.
swell
- ^ Y. Yarden, WJ Kuang, T. Yang-Feng et al.: Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand . In: The EMBO journal . tape 6 , no. November 11 , 1987, pp. 3341-3351 , PMID 2448137 , PMC 553789 (free full text).
- ↑ Zhuo Zhao, Shu-Min Lü, Geng-Si Xi: Temporal expression of c-kit in spermatogenesis of two grasshopper species. In: Insect Science. Volume 13, Number 6, December 2006, pp. 445-450 doi: 10.1111 / j.1744-7917.2006.00114.x
- ↑ Zhuo Zhao, Geng-Si Xi: The Special Expression and Comparison of the c-kit Protein in Spermatogenesis of Three Species of Locusts of Arcypteridae. In: Agricultural Sciences in China. Volume 6, Issue 7, July 2007, pp. 825-831. doi: 10.1016 / S1671-2927 (07) 60118-7
- ↑ JS Philo, J. Wen, J. Wypych, MG Schwartz, EA Mendiaz, KE Langley: Human stem cell factor dimer forms a complex with two molecules of the extracellular domain of its receptor, Kit . In: The Journal of biological chemistry . tape 271 , no. 12 , March 1996, p. 6895-6902 , PMID 8636116 .