Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins.
We have identified two platelet-derived growth factor (PDGF)-dependent autophosphorylation sites in the beta subunit of the human PDGF receptor (PDGF-R). The major site of phosphorylation (Tyr-857) corresponds to the major autophosphorylation site in many other tyrosine kinases. Tyr-751, which lies within the kinase insert region, is a second in vivo site and the major in vitro site. Immunoprecipitates of wild-type PDGF-Rs prepared from PDGF-treated cells contained a phosphatidylinositol (PI) 3 kinase activity and three specific polypeptides as well as the PDGF-R. Mutation of Tyr-751 to Phe or Gly, or mutation of the catalytic domain to abolish kinase activity, blocked association of the PDGF-R with the PI kinase and the three proteins. These results suggest that autophosphorylation in the kinase insert region triggers the binding of the activated PDGF-R to specific cellular proteins, including a PI kinase whose activity is known to be stimulated by PDGF. Thus autophosphorylation may play a novel role in signal transduction via the PDGF-R.
Kazlauskas
A
A
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Cooper
J A
JA
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004251:DNA Transposable Elements; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000302:isolation & purification; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D015398:Signal Transduction; D014357:Trypsin
D004251:DNA Transposable Elements; D010446:Peptide Fragments; D010748:Phosphopeptides; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D004247:DNA; D010770:Phosphotransferases; D011494:Protein Kinases; D019870:1-Phosphatidylinositol 4-Kinase; D017479:Receptors, Platelet-Derived Growth Factor; D014357:Trypsin