Phospho-c-Kit (Tyr568/570) Antibody #48347

c-Kit is a member of the subfamily of receptor tyrosine kinases that includes PDGF, CSF-1, and FLT3/flk-2 receptors (1,2). It plays a critical role in activation and growth in a number of cell types, including hematopoietic stem cells, mast cells, melanocytes, and germ cells (3). Upon binding with its stem cell factor (SCF) ligand, c-Kit undergoes dimerization/oligomerization and autophosphorylation. Activation of c-Kit results in the recruitment and tyrosine phosphorylation of downstream SH2-containing signaling components, including PLCγ, the p85 subunit of PI3 kinase, SHP2, and CrkL (4). Molecular lesions that impair the kinase activity of c-Kit are associated with a variety of developmental disorders (5), and mutations that constitutively activate c-Kit can lead to pathogenesis of mastocytosis and gastrointestinal stromal tumors (6). Tyr719 is located in the kinase insert region of the catalytic domain. c-Kit phosphorylated at Tyr719 binds to the p85 subunit of PI3 kinase in vitro and in vivo (7).

Tyr568 and Tyr570 are located in the juxtamembrane region of c-Kit. The phosphorylation of c-Kit at these sites is ligand induced and provides a docking site for recruitment of several adaptors/kinases, including Src, Cbl, SHP-1, APS, LNK, and SOSC6. Depending on which adaptor is bound, the outcome can lead to either cell survival and proliferation or c-Kit ubiquitination and degradation (8-13).