EGF receptor activation by GPCRs: an universal pathway reveals different versions.

About one decade ago has been demonstrated that G protein-coupled receptors (GPCRs) are able to utilize the epidermal growth factor (EGF) receptor (EGFR) as signalling intermediate. Thereby GPCRs are enabled to regulate cell growth, differentiation, and migration. A molecular mechanism for this process has been proposed that involves the activation of a distinct set of metalloproteases and the subsequent generation and release of particular members of the EGF peptide family which in turn activate the EGFR in an autocrine/paracrine manner. This model that allows GPCRs direct access to the signalling network of the EGFR family has emerged as a valid concept in a variety of cell types including cancer cells. The present review briefly summarizes the current knowledge but will be focussed on the ligand-dependency of EGFR transactivation. Several alternative mechanisms and novel aspects will be introduced. Using the example of head and neck squamous carcinoma, the potency of EGFR transactivation as a therapeutical target will be discussed.