Substrate phosphorylation specificity of the human c-kit receptor tyrosine kinase.
The chimeric EK-receptor (EK-R), consisting of the epidermal growth factor receptor (EGF-R) extracellular binding domain and p145c-kit cytoplasmic signal-generating sequences, was fully functional in forming high and low affinity EGF binding sites and in ligand-regulated receptor and substrate phosphorylation activities. Relative to EGF-R, EK-R activation stimulated kit-characteristic phosphorylation of human 293 fibroblast substrate polypeptides. Transient coexpression of EK-R with candidate substrates resulted in ligand-induced phosphorylation of phospholipase C gamma and guanosine triphosphatase-activating polypeptide. The RAF-1 serine/threonine kinase was shown to be associated with activated EK-R, but no tyrosine phosphorylation could be detected. The faithfulness of EK-R substrate phosphorylation specificity was confirmed with stem cell factor-stimulated p145c-kit.
Herbst
R
R
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Lammers
R
R
Schlessinger
J
J
Ullrich
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002678:Chimera; D004815:Epidermal Growth Factor / Q000378:metabolism; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000235:genetics
D020690:GTPase-Activating Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D010738:Type C Phospholipases