Early signaling pathways activated by c-Kit in hematopoietic cells

• Published in: International Journal of Biochemistry and Cell Biology 1999-10, Vol.31 (10), p.1053-1074
• Main Author: Linnekin, Diana
• Format: Article
• Language: English
• Subjects: Animals; Cytokines; Dimerization; DNA-Binding Proteins - metabolism; Growth factors; Hematopoiesis; Hematopoietic Stem Cells - metabolism; Humans; Janus Kinase 1; Mice; Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins c-kit - metabolism; Proto-Oncogene Proteins c-raf - metabolism; ras Proteins - metabolism; Signal Transduction; STAT1 Transcription Factor; Stem cell factor; Stem Cell Factor - metabolism; Structure-Activity Relationship; Trans-Activators - metabolism
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/S1357-2725(99)00078-3

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. Structure-function studies have begun to address the role of these signaling components in SCF-mediated responses. This review will focus on the biochemical mechanism of action of SCF in hematopoietic cells.