Stem cell factor (SCF, also called Steel factor or Kit ligand) is a growth factor that exists both as a membrane-bound and soluble form. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival, and differentiation of hematopoietic progenitors, melanocytes, and germ cells. It maps to chromosome 10 in the mouse and to chromosome 12 in humans. In both human, mouse, and rat, SCF is encoded by nine exons.
c-Kit is a receptor tyrosine kinase that binds stem cell factor (SCF). Structurally, c-Kit contains five immunoglobulin-like domains extracellularly and a catalytic domain divided into two regions by a 77 amino acid insert intracellularly. Studies in white spotting and steel mice have shown that functional SCF and c-Kit are critical in the survival and development of stem cells involved in hematopoiesis, pigmentation and reproduction. Mutations in c-Kit are associated with a variety of human diseases. Interaction of SCF with c-Kit rapidly induces receptor dimerization and increases in autophosphorylation activity.
Downstream of c-Kit, multiple signal transduction components are activated, including phosphatidylinositol-3-kinase, Src family members, the JAK/STAT pathway and the Ras–Raf–MAP kinase cascade
Although SCF may not be essential for the generation of hematopoiesis stem cells, numerous studies have shown that it prevents hematopoiesis stem cell apoptosis. Almost all cytokine combinations used to date for culturing hematopoiesis stem cells include SCF. SCF potentiates the greater ability of fetal liver hematopoiesis stem cells than adult hematopoiesis stem cells to undergo symmetric self-renewal in culture; this activity likely needs the cooperation of other factors. The membrane-bound form of SCF is also an adhesive molecule for hematopoiesis stem cells to the bone marrow environment, and an increased number of osteoclasts was associated with hematopoiesis stem cell mobilization. Receptor activator of nuclear factor (NF)-κB (RANK) ligand and cathepsin K mediate the cleavage of membrane-bound SCF; this decreases the abundance of SCF and, therefore, increases hematopoiesis stem cell mobilization. The involvement of SCF in survival, mobility, and possibly self-renewal of HSCs in culture and in the hematopoiesis stem cell niche likely reflects the complex relationship of different cell fates of hematopoiesis stem cells.
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