G protein-coupled receptor kinase 2 (GRK2) as an integrative signalling node in the regulation of cardiovascular function and metabolic homeostasis.

Autor: Mayor F Jr; Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain. Electronic address: fmayor@cbm.csic.es., Cruces-Sande M; Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain., Arcones AC; Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain., Vila-Bedmar R; Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain., Briones AM; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Farmacología, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain., Salaices M; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Farmacología, Universidad Autónoma de Madrid (UAM), 28029 Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain., Murga C; Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Universidad Autónoma de Madrid, 28049 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2018 Jan; Vol. 41, pp. 25-32. Date of Electronic Publication: 2017 Apr 04.
DOI: 10.1016/j.cellsig.2017.04.002
Abstrakt: G protein-coupled receptor kinase 2 (GRK2) is emerging as a pivotal signalling hub able to integrate different transduction cascades. This ability appears to underlie its central role in different physiological and pathological conditions. Key mediators of cardiovascular function (such as catecholamines or angiotensin II) and components of the systemic milieu altered in insulin resistance conditions converge in increasing GRK2 levels in diverse cardiovascular cell types. In turn, GRK2 would simultaneously modulate several cardiovascular regulatory pathways, including GPCR and insulin signalling cascades, NO bioavailability and mitochondrial function. This fact can help explain the contribution of increased GRK2 levels to maladaptive cardiovascular function and remodeling. It also unveils GRK2 as a link between cardiovascular pathologies and co-morbidities such as obesity or type 2 diabetes. On the other hand, enhanced GRK2 expression, as observed in adipose tissues, liver or skeletal muscle during insulin resistance-related pathologies, could modify the orchestration of GPCR and insulin signalling in these crucial metabolic organs, and contribute to key features of the obese and insulin-resistant phenotype.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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