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KIT (c-KIT) is a proto-oncogene and a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). KIT was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. KIT together with its ligand regulates growth and activation of a variety of hemopoietic and non-hemopoietic cells. Mutations in KIT are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Recently, deregulation of the KIT receptor TK by the prevalent activation loop mutation D816V has served as a focal point in therapeutic strategies aimed at curbing neoplastic mast cell growth. c-Kit is expressed in hematopoietic stem cells, germ cells, mast cells and gastrointestinal tract cajal cells. Upon binding of its ligand stem cell factor (SCF), c-kit dimerizes, resulting in receptor activation and autophosphorylation of various tyrosine residues including tyrosine 703 located on the cytoplasmic domain of the receptor. This modification allows docking of Grb2 and activation of the Ras/ERK signaling pathway. SCF/c-kit can activate multiple downstream signaling pathways including PI3K, PLC-gamma and JAK/STAT. c-kit receptor activation is essential for hematopoiesis, stem cell maintenance and gametogenesis.
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