G Protein‐Coupled Receptor Kinase 2 (GRK2) is Localized to Centrosomes and Mediates Epidermal Growth Factor‐Promoted Separation of Duplicated Centrosomes

Abstract

G protein‐coupled receptor kinases (GRKs) play a central role in regulating receptor signaling. Recent studies have suggested a broader role for these enzymes in regulating normal cellular functions. For example, GRK5 has been shown to localize in centrosomes and modulate cell cycle progression. In this study, we demonstrate that GRK2 is also localized to centrosomes. Similar to GRK5, the centrosomal localization of GRK2 is microtubule‐independent and it does not affect normal centrosome duplication. However, in contrast to GRK5, GRK2 is not involved in centrosome nucleation. Interestingly, knockdown of GRK2 inhibits epidermal growth factor (EGF)‐initiated separation of duplicated centrosomes during S phase in both HeLa cells and retinal pigment epithelial 1 (RPE1) cells. This EGFR‐GRK2 mediated process is dependent on the protein kinases MST‐2 and Nek2a but does not involve Polo‐like kinase 1 (PLK1). This separation during S phase results in enhanced centrosome amplification, resulting in a rise in the number of cells demonstrating aberrant duplicated centrosomes. Collectively, these findings demonstrate that GRK2 is localized in centrosomes and plays a central role in mitogen‐promoted centrosome separation.