Transactivation of the EGF Receptor: Is the PDGF Receptor an Unexpected Accomplice?

Signaling model of EGFR transactivation by crosstalk with a G protein-coupled receptor (GPCR). A mechanistic signaling model is described for heterologous GPCR coupling to an EGFR-dependent activation of the Ras/mitogen-activated protein kinase (MAPK) pathway (1). GPCR ligand-specific binding activates GPCR-Src- or calciumdependent tyrosine kinase- (CADTK, or Pyk-2) -dependent intracellular signals that promote the release from the cell surface of pro-HB-EGF through the matrix metalloproteinase-mediated proteolytic cleavage of this and other EGF-like growth factor precursors. Free, active HB-EGF binds to EGFR, leading to transactivation of the EGFR.