Background
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.
Alternative Names
KIT; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; PBT; SCFR; C-Kit; CD117; mast/stem cell growth factor receptor Kit; p145 c-kit; proto-oncogene c-Kit; piebald trait protein; soluble KIT variant 1; tyrosine-protein kinase Kit; proto-oncogene tyrosine-protein kinase Kit; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene-like protein
Function
Tyrosine-protein kinase, as the cell surface receptor of cytokine KITLG/SCF, plays an important role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gamete formation, mast cell development, migration and function, and melanogenesis . After the combination of KITLG/SCF, KIT can activate a variety of signal pathways. Phosphorylate PIK3R1, PLCG1, SH2B2/APS and CBL. The AKT1 signaling pathway is activated by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals through activation of GRB2 and RAS, RAF1, and MAPK1/ERK2 and/or MAPK3/ERK1. Promote the activation of STAT family members STAT1, STAT3, STAT5A, and STAT5B. The activation of PLCG1 leads to the production of cell signaling molecules triglycerides and inositol 1,4,5-triphosphate. KIT signal is regulated by the rapid internalization and degradation of protein phosphatase and receptor. The activated KIT can promote the phosphorylation of protein phosphatase PTPN6/SHP-1 and PTPRU, and the phosphorylation of transcription factors STAT1, STAT3, STAT5A and STAT5B. Promote the phosphorylation of PIK3R1, CBL, CRK (CRK-ii subtype), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.
Post-translational modifications
Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation. Autophosphorylated on tyrosine residues. KITLG/SCF binding enhances autophosphorylation. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase activity is down-regulated by phosphorylation on serine residues by protein kinase C family members. Phosphorylation at Tyr-568 is required for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, Tyr-823 and Tyr-936 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-823 and Tyr-936 is important for interaction with GRB7.