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G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation

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 progressio...

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Autores principales: So, Christopher H., Michal, Allison, Komolov, Konstantin E., Luo, Jiansong, Benovic, Jeffrey L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771943/
https://www.ncbi.nlm.nih.gov/pubmed/23904266
http://dx.doi.org/10.1091/mbc.E13-01-0013
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author So, Christopher H.
Michal, Allison
Komolov, Konstantin E.
Luo, Jiansong
Benovic, Jeffrey L.
author_facet So, Christopher H.
Michal, Allison
Komolov, Konstantin E.
Luo, Jiansong
Benovic, Jeffrey L.
author_sort So, Christopher H.
collection PubMed
description 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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spelling pubmed-37719432013-11-30 G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation So, Christopher H. Michal, Allison Komolov, Konstantin E. Luo, Jiansong Benovic, Jeffrey L. Mol Biol Cell Articles 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. The American Society for Cell Biology 2013-09-15 /pmc/articles/PMC3771943/ /pubmed/23904266 http://dx.doi.org/10.1091/mbc.E13-01-0013 Text en © 2013 So et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
So, Christopher H.
Michal, Allison
Komolov, Konstantin E.
Luo, Jiansong
Benovic, Jeffrey L.
G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
title G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
title_full G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
title_fullStr G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
title_full_unstemmed G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
title_short G protein–coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
title_sort g protein–coupled receptor kinase 2 (grk2) is localized to centrosomes and mediates epidermal growth factor–promoted centrosomal separation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771943/
https://www.ncbi.nlm.nih.gov/pubmed/23904266
http://dx.doi.org/10.1091/mbc.E13-01-0013
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