Editors' ChoiceReceptor Transactivation

Crosstalk at the Membrane

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Science's STKE  11 Sep 2001:
Vol. 2001, Issue 99, pp. tw322
DOI: 10.1126/stke.2001.99.tw322

The epidermal growth factor receptor (EGFR) can become activated when other membrane receptors bind to their cognate ligands. For example, when platelet-derived growth factor (PDGF) binds to its receptor (PDGFR), the EGFR becomes phosphorylated on tyrosine. Saito et al. report that this transactivation may occur at the plasma membrane of vascular smooth muscle cell. A complex containing endogenous EGFR and PDGFR subunits was detected, even in the absence of PDGF treatment. Stimulation of cells with PDGF caused simultaneous activation of both receptor types, but did not increase heterodimer formation. PDGFR kinase activity was not required for EGFR transactivation. Because inhibition of Src kinase activity blocked heterodimer formation, the authors propose that Src phosphorylates a protein in the receptor complex that is critical for maintaining heterodimer association. The proposed model suggests that PDGF induces homodimerization of the PDGFR, but that associated EGFRs may not necessarily homodimerize.

Y. Saito, J. Haendeler, Y. Hojo, K. Yamamoto, B.C. Berk, Receptor heterodimerization: Essential mechanism for platelet-derived growth factor-induced epidermal growth factor receptor transactivation. Mol. Cell Biol. 21, 6387-6394 (2001). [Abstract] [Full Text]

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