title: Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection.
abstract: The epidermal growth factor receptor (EGFR) family comprises the ErbB1 (EGFR) and ErbB4 receptors as well as the 'co-receptors' ErbB2 (which does not bind EGF ligands) and ErbB3 (which lack tyrosine kinase activity). This family of receptors is essential for cardiac development, myocardial, renal and vascular function, and cardiac responses to physiological and pathological perturbations. The EGFR appears critical in protecting cardiac cells from injury, while considerable attention has focussed on neuregulin/ErbB4 signalling in potentially ameliorating cardiomyopathy/heart failure. Indeed, the EGFRs provide a signalling nexus, upon which multiple cardioprotective stimuli appear to converge, including ischaemic preconditioning and various G protein-coupled receptors (opioid, muscarinic, adenosine, adrenergic, bradykinin, sphingosine 1-phosphate). These stimuli engage the EGFR axis (in a process referred to as transactivation) in differing ways, involving both G protein-dependent and -independent mechanisms, to promote myocardial cell survival during and following ischaemia/infarction. Elucidating the molecular processes that underpin EGFR transactivation and mediate cardiac protection will advance our understanding of the intrinsic capacity of the heart to withstand pathological insult. It should also reveal new approaches to facilitate cardioprotective therapy to limit damage during and following myocardial ischaemia/infarction, which despite intense investigation remains an unrealised, yet highly desirable, clinical goal. This review focuses on the cardiovascular functions of the EGFR, its role in cardioprotection, and the potential influences of common disease states on this signalling.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: m.reichelt@uq.edu.au.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Reichelt
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Shannon
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Walter G
authors.initials: WG
authors.lastname: Thomas
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4017, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Headrick
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D066246:ErbB Receptors / Q000819:agonists / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006331:Heart Diseases / Q000378:metabolism; D006801:Humans; D019194:Ischemic Preconditioning; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D019390:Arrestins; D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D019204:GTP-Binding Proteins
keywords: Cardioprotection; EGFR; ErbB; G protein-coupled receptors; Ischaemia-reperfusion; Preconditioning; Transactivation