title: Unravelling the molecular complexity of GPCR-mediated EGFR transactivation using functional genomics approaches.
abstract: To influence physiology and pathophysiology, G protein-coupled receptors (GPCRs) have evolved to appropriate additional signalling modalities, such as activation of adjacent membrane receptors. Epidermal growth factor receptors (EGFRs) mediate growth and remodelling actions of GPCRs, although the precise network of gene products and molecular cascades linking GPCRs to EGFRs (termed EGFR transactivation) remains incomplete. In this review, we describe the current view of GPCR-EGFR transactivation, identifying the established models of receptor cross-talk. We consider the limitations in our current knowledge, and propose that recent advances in molecular and cell biology technology, including functional genomics approaches, will allow a renewed focus of efforts to understand the mechanism underlying EGFR transactivation. Using an unbiased approach for identification of the molecules required for GPCR-mediated EGFR transactivation will provide a contemporary and more complete representation from which to extrapolate therapeutic control in diseases from cardiovascular remodelling to cancer.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St Lucia, Qld, Australia; Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia; Department of Pathology, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Amee J
authors.initials: AJ
authors.lastname: George
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
authors.forename: Walter G
authors.initials: WG
authors.lastname: Thomas
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D023281:Genomics; D006801:Humans; D020239:Receptor Cross-Talk; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D043562:Receptors, G-Protein-Coupled; D066246:ErbB Receptors
keywords: G protein-coupled receptor; RNA interference; cancer; cardiac hypertrophy; cardiovascular disease; epidermal growth factor receptor; functional genomics; receptor cross-talk; signalling; transactivation