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

Mol Cell Endocrinol. 2011 Jan 15;331(2):222-31. doi: 10.1016/j.mce.2010.04.008. Epub 2010 Apr 14.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinoma / metabolism
  • Carcinoma / therapy
  • Carcinoma, Squamous Cell
  • Cell Growth Processes / physiology
  • Cell Movement / physiology
  • ErbB Receptors / metabolism*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / therapy
  • Humans
  • Ligands
  • Metalloproteases / metabolism
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / therapy
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Ligands
  • Receptors, G-Protein-Coupled
  • ErbB Receptors
  • Metalloproteases