The epidermal growth factor receptor associates with and recruits phosphatidylinositol 3-kinase to the platelet-derived growth factor β receptor

A. A. Habib, T. Hognason, J. Ren, K. Stefansson, R. R. Ratan

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40 Scopus citations

Abstract

Receptor tyrosine kinases are classified into subfamillies, which are believed to function independently, with heterodimerization occurring only within the same subfamily. In this study, we present evidence suggesting a direct interaction between the epidermal growth factor (EGF) receptor (EGFR) and the platelet-derived growth factor β (PDGFβ) receptor (PDGFβR), members of different receptor tyrosine kinase subfamilies. We find that the addition of EGF to COS-7 cells and to human foreskin Hs27 fibroblasts results in a rapid tyrosine phosphorylation of the PDGFβR and results in the recruitment of phosphatidylinomitol 3-kinase to the PDGFβR. In R1hER cells, which overexpress the EGFR, we find ligand-independent tyrosine phosphorylation of the PDGFβR and constitutive binding of a substantial amount of PI-3 kinase activity to it, mimicking the effect of ligand in untransfected cells. In support of the possibility that this may be a direct interaction, we show that the two receptors can be coimmunoprecipitated from untransfected Hs27 fibroblasts and from COS-7 cells. This association can be reconstituted by introducing the two receptors into 293 EBNA cells. The EGFR/PDGFβR association is ligand-independent in all cell lines tested. We also demonstrate that the fraction of PDGFβR bound to the EGFR in R1hER cells undergoes an EGF-induced mobility shift on Western blots indicative of phosphorylation. Our findings indicate that direct interactions between receptor tyrosine kinases classified under different subfamilies may be more widespread than previously believed.

Original languageEnglish (US)
Pages (from-to)6885-6891
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number12
DOIs
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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