c-Kit - The Novel Receptor: Physiological Roles, Downstream Signaling and Implications in Cancer

Abstract

The belief that adult mammalian heart lacks regenerative potential was challenged by the identification of c-kit positive Cardiac Progenitor Cells (CPCs) in the heart. SCIPIO; a phase I clinical trial; has shown that autologous c-kit positive CPCs improve cardiac function and quality of life when transplanted into ischemic heart disease patients. c-Kit is a type III receptor tyrosine kinase and a common stem cell antigen. Stem Cell Factor (SCF) is the only known ligand for c-kit. Activation of this membrane bound receptor is known to play a crucial role in many physiological processes like hematopoiesis, immune regulation, pigmentation, gametogenesis, intestinal motility, vasculogenesis, lung and brain development. Likewise, aberrant c-kit stimulation results in several pathological conditions, including tumors of the gut, blood, lung, breast, germ cells, melanocytes and mast cells. Several pro-growth, pro-survival signaling pathways like the MAPK, PI-3K and the phospholipase C and D pathways are involved in mediating the downstream effects, following the activation of this receptor. The goal of this article is to provide a comprehensive review of the structure, function, signaling mechanisms of c-kit activation and its role in normal and pathological conditions.