c-Kit

Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.

Defects in Kit are the cause of the white-spotting phenotype (W). White-spotting variants induces severe effects on pigmentation, gametogenesis and hematopoiesis. Mice homozygous for W42 die perinatally of macrocytic anemia.

Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation (By similarity).

Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation of isoform 1 and isoform 2. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF, while isoform 2 requires stimulation by KITLG/SCF for phosphorylation (in vitro). Phosphorylation of Tyr-573 is required for interaction with PTPN6/SHP-1. Phosphorylation of Tyr-571 is required for interaction with PTPN11/SHP-2. Phosphorylated tyrosine residues are important for interaction with specific binding partners.

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Isoform 1 and isoform 2 are detected in bone marrow cells, spermatogonia and spermatocytes, but not in round spermatids, elongating spermatids and spermatozoa. Isoform 3 is detected in round spermatids, elongating spermatids and spermatozoa, but not in spermatogonia and spermatocytes (at protein level). Isoform 1 is widely expressed and detected in fetal liver and bone marrow. Isoform 3 is detected in bone marrow cells enriched in hematopoietic stem cells.

• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• Isoform 2
• Cell membrane
• Single-pass type I membrane protein
• Isoform 3
• Cytoplasm
• Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.

CD117, Sl, Kit, Mast/stem cell growth factor receptor Kit, SCFR, Proto-oncogene c-Kit, Tyrosine-protein kinase Kit

• entrezGene:16590
• swissprot:P05532

Proteins

Oncology

• Immunology & Infectious Disease

109343Da