G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub

  • Cell Mol Life Sci. 2019 Nov;76(22):4423-4446. doi: 10.1007/s00018-019-03274-3.
Petronila Penela  1  2  3 ,  Catalina Ribas  1  2  3 ,  Francisco Sánchez-Madrid  2  3  4 ,  Federico Mayor Jr  5  6  7
Affiliations
  • 1. Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (UAM-CSIC), Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, 28049, Madrid, Spain.
  • 2. Instituto de Investigación Sanitaria La Princesa, 28006, Madrid, Spain.
  • 3. CIBER de Enfermedades Cardiovasculares, ISCIII (CIBERCV), 28029, Madrid, Spain.
  • 4. Cell-Cell Communication Laboratory, Vascular Pathophysiology Area, Centro Nacional Investigaciones Cardiovasculares (CNIC), 28029, Madrid, Spain.
  • 5. Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (UAM-CSIC), Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, 28049, Madrid, Spain. [email protected].
  • 6. Instituto de Investigación Sanitaria La Princesa, 28006, Madrid, Spain. [email protected].
  • 7. CIBER de Enfermedades Cardiovasculares, ISCIII (CIBERCV), 28029, Madrid, Spain. [email protected].
PMID: 31432234 DOI: 10.1007/s00018-019-03274-3
Abstract

Accumulating evidence indicates that G protein-coupled receptor kinase 2 (GRK2) is a versatile protein that acts as a signaling hub by modulating G protein-coupled receptor (GPCR) signaling and also via phosphorylation or scaffolding interactions with an extensive number of non-GPCR cellular partners. GRK2 multifunctionality arises from its multidomain structure and from complex mechanisms of regulation of its expression levels, activity, and localization within the cell, what allows the precise spatio-temporal shaping of GRK2 targets. A better understanding of the GRK2 interactome and its modulation mechanisms is helping to identify the GRK2-interacting proteins and its substrates involved in the participation of this kinase in different cellular processes and pathophysiological contexts.

Keywords
GPCR; GRK2; HDAC6; Interactome; Phosphorylation.