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.
Liebmann
Claus
C
Center of Molecular Biomedicine (CMB), Institute of Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Hans-Knöll-Str. 2, D-07745 Jena, Germany. Claus.Liebmann@uni-jena.de
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy; D002294:Carcinoma, Squamous Cell; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000628:therapy; D006801:Humans; D008024:Ligands; D045726:Metalloproteases / Q000378:metabolism; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000628:therapy; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D066246:ErbB Receptors; D045726:Metalloproteases