G Protein-coupled Receptor Kinase 2 (GRK2) is Localized to Centrosomes and Mediates Epidermal Growth Factor-promoted Centrosomal Separation

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2013 Aug 2

PMID 23904266

Citations 12

Authors

Christopher H So

Allison Michal

Konstantin E Komolov

Jiansong Luo

Jeffrey L Benovic

Affiliations

Soon will be listed here.

Abstract

G protein-coupled receptor kinases (GRKs) play a central role in regulating receptor signaling, but recent studies suggest a broader role in modulating normal cellular functions. For example, GRK5 has been shown to localize to centrosomes and regulate microtubule nucleation and cell cycle progression. Here we demonstrate that GRK2 is also localized to centrosomes, although it has no role in centrosome duplication or microtubule nucleation. Of interest, knockdown of GRK2 inhibits epidermal growth factor receptor (EGFR)-mediated separation of duplicated centrosomes. This EGFR/GRK2-mediated process depends on the protein kinases mammalian STE20-like kinase 2 (Mst2) and Nek2A but does not involve polo-like kinase 1. In vitro analysis and dominant-negative approaches reveal that GRK2 directly phosphorylates and activates Mst2. Collectively these findings demonstrate that GRK2 is localized to centrosomes and plays a central role in mitogen-promoted centrosome separation most likely via its ability to phosphorylate Mst2.

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