Early signaling pathways activated by c-Kit in hematopoietic cells.
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.
Linnekin
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Basic Research Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. dlinnekin@mail.ncifcrf.gov
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D053613:Janus Kinase 1; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D019089:Stem Cell Factor; D015534:Trans-Activators; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins