Early signaling pathways activated by c-Kit in hematopoietic cells

Int J Biochem Cell Biol. 1999 Oct;31(10):1053-74. 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.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • 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
  • STAT1 Transcription Factor
  • Signal Transduction*
  • Stem Cell Factor / metabolism*
  • Structure-Activity Relationship
  • Trans-Activators / metabolism
  • ras Proteins / metabolism


  • DNA-Binding Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Stat1 protein, mouse
  • Stem Cell Factor
  • Trans-Activators
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • ras Proteins