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Sci. Signal., 15 May 2012
Vol. 5, Issue 224, p. pt3
[DOI: 10.1126/scisignal.2003098]


Roles of GRK2 in Cell Signaling Beyond GPCR Desensitization: GRK2-HDAC6 Interaction Modulates Cell Spreading and Motility

Petronila Penela1,2*, Vanesa Lafarga1,2, Olga Tapia3, Verónica Rivas1,2, Laura Nogués1,2, Elisa Lucas1,2, Rocío Vila-Bedmar1,2, Cristina Murga1,2, and Federico Mayor Jr.1,2*{dagger}

1 Departamento de Biología Molecular and Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, 28049 Madrid, Spain.
2 Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain.
3 Department of Anatomy and Cell Biology, University of Cantabria-IFIMAV, Santander, Spain.

{dagger} Presenter. E-mail: fmayor{at}

A Presentation from the Cell Signaling Networks Conference and 13th IUBMB Conference, Mérida, Yucatán, México, 22 to 27 October 2011.

Abstract: G protein–coupled receptor kinase 2 (GRK2) is a ubiquitous, essential protein kinase that is emerging as an integrative node in many signaling networks. Moreover, changes in GRK2 abundance and activity have been identified in several inflammatory, cardiovascular disease, and tumor contexts, suggesting that those alterations may contribute to the initiation or development of pathologies. GRKs were initially identified as key players in the desensitization and internalization of multiple G protein–coupled receptors (GPCRs), but GRK2 also phosphorylates several non-GPCR substrates and dynamically associates with a variety of proteins related to signal transduction. Ongoing research in our laboratory is aimed at understanding how specific GRK2 interactomes are orchestrated in a stimulus-, context-, or cell type–specific manner. We have recently identified an interaction between GRK2 and histone deacetylase 6 (HDAC6) that modulates cell spreading and motility. HDAC6 is a major cytoplasmic a-tubulin deacetylase that is involved in cell motility and adhesion. GRK2 dynamically and directly associates with and phosphorylates HDAC6 to stimulate its a-tubulin deacetylase activity at specific cellular localizations, such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility. GRK2-HDAC6–mediated regulation of tubulin acetylation also modulates cellular spreading. This GRK2-HDAC6 functional interaction may have important implications in pathological contexts related to epithelial cell migration.

* Corresponding authors. E-mail: fmayor{at} (F.M.); ppenela{at} (P.P.)

Citation: P. Penela, V. Lafarga, O. Tapia, V. Rivas, L. Nogués, E. Lucas, R. Vila-Bedmar, C. Murga, F. Mayor, Jr., Roles of GRK2 in Cell Signaling Beyond GPCR Desensitization: GRK2-HDAC6 Interaction Modulates Cell Spreading and Motility. Sci. Signal. 5, pt3 (2012).

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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882