Cell
Volume 58, Issue 6, 22 September 1989, Pages 1121-1133
Journal home page for Cell

Article
Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins

https://doi.org/10.1016/0092-8674(89)90510-2Get rights and content

Abstract

We have identified two platelet-derived growth factor (PDGF)-dependent autophosphorylation sites in the β 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.

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