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Triple membrane-passing signal mechanism of EGFR transactivation. GPCR-induced EGFR transactivation involves as key elements pro-HB-EGF, an EGF-like growth factor precursor, and a metalloproteinase activity that is induced upon G-protein activation. Therefore, this new mechanistic concept for ligand-dependent GPCR-EGFR cross-talk entails three membrane-passing signals and couples G-protein signalling to activation of the Ras-MAPK pathway.
