SCF-R Antibody – Rat Monoclonal

The c-Kit proto-oncogene is the cellular homolog of the transforming gene of a feline retrovirus (v-Kit). The c-kit protein includes characteristics of a protein kinase transmembrane receptor. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Function: Tyrosine-protein kinase that acts as 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. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.17 Ref.19

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.11

Enzyme regulation: Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation.

Subunit structure: Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with DOK1 and TEC

By similarity. Interacts with the protein kinase FES/FPS. Interacts with PLCG1. Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3 catalytic subunit. Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.15

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.11. Isoform 2: Cell membrane; Single-pass type I membrane protein Ref.11. Isoform 3: Cytoplasm. Note: Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head

By similarity. Ref.11

Tissue specificity: 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. Ref.3 Ref.11 Ref.18

Post-translational modification: Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation

By similarity. Ref.11Autophosphorylated 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. Ref.9 Ref.11

Involvement in disease: 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. Ref.9 Ref.10 Ref.11 Ref.13 Ref.15 Ref.21 Ref.22 Ref.23

Miscellaneous: Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions.

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.Contains 5 Ig-like C2-type (immunoglobulin-like) domains.Contains 1 protein kinase domain.