Signal transduction via the stem cell factor receptor/c-Kit.
Together with its ligand, stem cell factor, the receptor tyrosine kinase c-Kit is a key controlling receptor for a number of cell types, including hematopoietic stem cells, mast cells, melanocytes and germ cells. Gain-of-function mutations in c-Kit have been described in a number of human cancers, including testicular germinomas, acute myeloid leukemia and gastrointestinal stromal tumors. Stimulation of c-Kit by its ligand leads to dimerization of receptors, activation of its intrinsic tyrosine kinase activity and phosphorylation of key tyrosine residues within the receptor. These phosphorylated tyrosine residues serve as docking sites for a number of signal transduction molecules containing Src homology 2 domains, which will thereby be recruited to the receptor and activated many times through phosphorylation by the receptor. This review discusses our current knowledge of signal transduction molecules and signal transduction pathways activated by c-Kit and how their activation can be connected to the physiological outcome of c-Kit signaling.
Rönnstrand
L
L
Experimental Clinical Chemistry,Wallenberg Laboratory, Lund University,Malmö University Hospital, 205 02, Malmö, Sweden. Lars.Ronnstrand@expklkemi.mas.lu.se
D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D019281:Dimerization; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010766:Phosphorylation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014443:Tyrosine / Q000737:chemistry; D018909:src Homology Domains
D008024:Ligands; D020033:Protein Isoforms; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit