KIT Blocking Peptide (Center)

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. [provided by RefSeq, Jul 2008]

Kit: a receptor tyrosine kinase and a member of the subfamily that includes PDGF, CSF-1 and FLT-3/flk-2 receptors. Receptor for stem cell factor. Plays a critical role in hematopoietic stem cell, mast cell, melanocyte and germ cell development. Ligand binding induces autophosphorylation, dimerization and activation, leading to the recruitment and phosphorylation of downstream SH2-containing signaling components including PLC-gamma, PI3 kinase p85, SHP2 and CrkL, linking c-Kit to various cell signaling pathways. Molecular lesions that impair the kinase activity of c-Kit are associated with a variety of developmental disorders, while mutations that constitutively activate c-Kit can lead to hyperplasia and tumorigenesis. Activating mutations cause >90% of gastrointestinal stromal tumors (GIST); successfully treated with inhibitors Gleevec (imatinib, Glivec) and Sutent (Sutinib, SU11248). Activating mutations also induce mastocytosis. Autocrine/paracrine stimulation may drive some lung and other tumors. Loss of expression associated with melanoma progression. Familial loss of function mutations cause piebaldism, with defects in hair and skin pigmentation due to lack of melanocytes.

Protein type: Protein kinase, TK; Oncoprotein; Membrane protein, integral; EC 2.7.10.1; Kinase, protein; Protein kinase, tyrosine (receptor); TK group; PDGFR family

Chromosomal Location of Human Ortholog: 4q12

Cellular Component: extracellular space; plasma membrane

Molecular Function: cytokine binding; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein homodimerization activity; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; transmembrane receptor protein tyrosine kinase activity

Biological Process: actin cytoskeleton reorganization; activation of MAPK activity; cytokine and chemokine mediated signaling pathway; dendritic cell cytokine production; detection of mechanical stimulus involved in sensory perception of sound; embryonic hemopoiesis; erythrocyte differentiation; gut development; hemopoiesis; immature B cell differentiation; inflammatory response; lamellipodium biogenesis; male gonad development; MAPKKK cascade; mast cell chemotaxis; mast cell cytokine production; mast cell degranulation; melanocyte differentiation; ovarian follicle development; peptidyl-tyrosine phosphorylation; phosphoinositide-mediated signaling; pigmentation; positive regulation of JAK-STAT cascade; positive regulation of MAPKKK cascade; positive regulation of phosphoinositide 3-kinase activity; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of transcription factor activity; positive regulation of tyrosine phosphorylation of Stat1 protein; positive regulation of tyrosine phosphorylation of Stat3 protein; positive regulation of tyrosine phosphorylation of Stat5 protein; protein amino acid autophosphorylation; regulation of cell proliferation; regulation of cell shape; regulation of phosphoinositide 3-kinase cascade; signal transduction; spermatogenesis; stem cell differentiation; stem cell maintenance; T cell differentiation

Disease: Gastrointestinal Stromal Tumor; Mast Cell Disease; Piebald Trait; Testicular Germ Cell Tumor