Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection. (February 2017)

• Record Type: Journal Article
• Authors: Reichelt, Melissa E.; O'Brien, Shannon; Thomas, Walter G.; Headrick, John P.
• Is Part Of: International journal of biochemistry & cell biology. Volume 83(2017)
• Page Start: 97
• Page End: 110
• Publication Date: 2017-02
• Subjects: EGFR -- ErbB -- Cardioprotection -- G protein-coupled receptors -- Ischaemia-reperfusion -- Preconditioning -- Transactivation; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.12.014
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: ErbB1/EGFR can be activated by multiple GPCRs through a process termed 'transactivation'. EGFR acts as a nexus for GPCR-mediated protective signalling. EGFR localisation to caveolae microdomains is critical to signal transduction. EGFRs appear to be a critical determinant of myocardial tolerance to ischaemia-reperfusion. Signalling mediators downstream to EGFR include arrestins, PI3K, PKB/Akt, ERK and PKC. EGFR signalling is perturbed in ischaemic heart disease, hypertrophy/heart failure, diabetes and obesity/dyslipidaemia. Despite a predominance of evidence for a protective role for the EGFR, EGFR over-activity may be detrimental specifically in the context of vascular injury. 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.