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Michal AM , So CH , Beeharry N , Shankar H , Mashayekhi R , Yen TJ , Benovic JL
G Protein-coupled Receptor Kinase 5 Is Localized to Centrosomes and Regulates Cell Cycle Progression
Journal of Biological Chemistry. 2012 Feb;287(9) :6928-6940
PMID: WOS:000300791800077 PMCID: PMC3307296
AbstractG protein-coupled receptor kinases (GRKs) are important regulators of G protein-coupled receptor function and mediate receptor desensitization, internalization, and signaling. While GRKs also interact with and/or phosphorylate many other proteins and modify their function, relatively little is known about the cellular localization of endogenous GRKs. Here we report that GRK5 co-localizes with gamma-tubulin, centrin, and pericentrin in centrosomes. The centrosomal localization of GRK5 is observed predominantly at interphase and although its localization is not dependent on microtubules, it can mediate microtubule nucleation of centrosomes. Knockdown of GRK5 expression leads to G2/M arrest, characterized by a prolonged G2 phase, which can be rescued by expression of wild type but not catalytically inactive GRK5. This G2/ M arrest appears to be due to increased expression of p53, reduced activity of aurora A kinase and a subsequent delay in the activation of polo-like kinase 1. Overall, these studies demonstrate that GRK5 is localized in the centrosome and regulates microtubule nucleation and normal cell cycle progression.
NotesMichal, Allison M. So, Christopher H. Beeharry, Neil Shankar, Haripriya Mashayekhi, Rouzbeh Yen, Timothy J. Benovic, Jeffrey L. National Institutes of Health[GM44944, CA129626, GM86877, GM44762]; Canadian Heart & Stroke Foundation; DOD[W81XWH-11-1-0201]; Commonwealth of Pennsylvania; Greenberg Fund; [CA06927] This work was supported, in whole or in part, by National Institutes of Health Grants GM44944 and CA129626 (to J.L.B.) and GM86877 and GM44762 (to T.J.Y.).Supported in part by a postdoctoral fellowship from the Canadian Heart & Stroke Foundation.Supported by a core grant (CA06927), the DOD (W81XWH-11-1-0201), an appropriation from the Commonwealth of Pennsylvania, and the Greenberg Fund. 45 Amer soc biochemistry molecular biology inc Bethesda 899cq