title: ErbB/integrin signaling interactions in regulation of myocardial cell-cell and cell-matrix interactions.
abstract: Neuregulin (Nrg)/ErbB and integrin signaling pathways are critical for the normal function of the embryonic and adult heart. Both systems activate several downstream signaling pathways, with different physiological outputs: cell survival, fibrosis, excitation-contraction coupling, myofilament structure, cell-cell and cell-matrix interaction. Activation of ErbB2 by Nrg1β in cardiomycytes or its overexpression in cancer cells induces phosphorylation of FAK (Focal Adhesion Kinase) at specific sites with modulation of survival, invasion and cell-cell contacts. FAK is also a critical mediator of integrin receptors, converting extracellular matrix alterations into intracellular signaling. Systemic FAK deletion is lethal and is associated with left ventricular non-compaction whereas cardiac restriction in adult hearts is well tolerated. Nevertheless, these hearts are more susceptible to stress conditions like trans-aortic constriction, hypertrophy, and ischemic injury. As FAK is both downstream and specifically activated by integrins and Nrg-1β, here we will explore the role of FAK in the heart as a protective factor and as possible mediator of the crosstalk between the ErbB and Integrin receptors. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland. laura.pentassuglia@unibas.ch
authors.forename: Laura
authors.initials: L
authors.lastname: Pentassuglia
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Sawyer
mesh_terms: D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D005109:Extracellular Matrix / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D018739:Oncogene Proteins v-erbB / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D016023:Integrins; D007527:Isoenzymes; C094131:NRG1 protein, human; D020890:Neuregulin-1; D018739:Oncogene Proteins v-erbB; D051416:Focal Adhesion Protein-Tyrosine Kinases