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

So, Christopher H.; Michal, Allison M.; Komolov, Konstantin E.; Luo, Jiansong; Benovic, Jeffrey L.

doi:10.1091/mbc.e13-01-0013

Cited by 20 publications

(19 citation statements)

References 71 publications

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“…As the centrosomes separate further, more and more chromosomes become available to the MTs emanating from both poles, and this increases the chances of correct syntelic attachments due to symmetric outgrowth of MTs from both spindle poles [94]. In line with these observations and models [89,90,92,94,95], EGF-induced early centrosome separation promotes a faster mitotic progression with fewer chromosome segregation errors [92]. Induction of early centrosome separation either by addition of EGF to the medium or by expression of the EGFR decreases the requirement of Eg5 for mitotic progression [92].…”

Section: Timing Is Everythingsupporting

confidence: 61%

Separate to operate: control of centrosome positioning and separation

Agircan

Schiebel

Mardin

2014

Phil. Trans. R. Soc. B

103

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The centrosome is the main microtubule (MT)-organizing centre of animal cells. It consists of two centrioles and a multi-layered proteinaceous structure that surrounds the centrioles, the so-called pericentriolar material. Centrosomes promote de novo assembly of MTs and thus play important roles in Golgi organization, cell polarity, cell motility and the organization of the mitotic spindle. To execute these functions, centrosomes have to adopt particular cellular positions. Actin and MT networks and the association of the centrosomes to the nuclear envelope define the correct positioning of the centrosomes. Another important feature of centrosomes is the centrosomal linker that connects the two centrosomes. The centrosome linker assembles in late mitosis/G1 simultaneously with centriole disengagement and is dissolved before or at the beginning of mitosis. Linker dissolution is important for mitotic spindle formation, and its cell cycle timing has profound influences on the execution of mitosis and proficiency of chromosome segregation. In this review, we will focus on the mechanisms of centrosome positioning and separation, and describe their functions and mechanisms in the light of recent findings.

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Section: Timing Is Everythingsupporting

confidence: 61%

Separate to operate: control of centrosome positioning and separation

Agircan

Schiebel

Mardin

2014

Phil. Trans. R. Soc. B

103

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“…With the growing understanding of centrosome disjunction mechanisms, the reason for this observation was revisited with discovery that EGF regulates association of Nek2 with centrosomes via Mst2, Akt, and PI3K (Mardin et al, 2013 ). Further studies not only confirmed the role of Mst2 and Nek2 in EGF-mediated centrosome separation, but also demonstrated a role for the G-protein-coupled receptor kinase 2 (GRK2) in phosphorylating Mst2 in response to EGF (So et al, 2013 ). This occurs on two of three sites that are also phosphorylated by Plk1, hence Mst2 provides a point of integration of extracellular signals from EGFR with internal signals of mitotic progression from Plk1.…”

Section: Nek Kinases In Centrosome Disjunctionmentioning

confidence: 90%

Mitotic Regulation by NEK Kinase Networks

Fry

Bayliss

Roig

2017

Front. Cell Dev. Biol.

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Genetic studies in yeast and Drosophila led to identification of cyclin-dependent kinases (CDKs), Polo-like kinases (PLKs) and Aurora kinases as essential regulators of mitosis. These enzymes have since been found in the majority of eukaryotes and their cell cycle-related functions characterized in great detail. However, genetic studies in another fungal species, Aspergillus nidulans, identified a distinct family of protein kinases, the NEKs, that are also widely conserved and have key roles in the cell cycle, but which remain less well studied. Nevertheless, it is now clear that multiple NEK family members act in networks to regulate specific events of mitosis, including centrosome separation, spindle assembly and cytokinesis. Here, we describe our current understanding of how the NEK kinases contribute to these processes, particularly through targeted phosphorylation of proteins associated with the microtubule cytoskeleton. We also present the latest findings on molecular events that control the activation state of the NEKs and how these are revealing novel modes of enzymatic regulation relevant not only to other kinases but also to pathological mechanisms of disease.

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“…Addition of EGF to the culture medium or overexpression of EGFR induces premature centrosome separation, presumably by activating the Mst2-Nek2A module in S phase (Mardin et al, 2013). G protein-coupled receptor kinase 2 (GRK2) has been found at centrosomes and may be involved in EGFR-mediated centrosome separation (So et al, 2013). Upon EGF addition, GRK2 phosphorylates and activates Mst2, leading to the initiation of centrosome disjunction.…”

Section: Centrosome Dynamicsmentioning

confidence: 99%

Mitotic kinase cascades orchestrating timely disjunction and movement of centrosomes maintain chromosomal stability and prevent cancer

2015

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Centrosomes are microtubule-organizing centers that duplicate in S phase to form bipolar spindles that separate duplicated chromosomes faithfully into two daughter cells during cell division. Recent studies show that proper timing of centrosome dynamics, the disjunction and movement of centrosomes, is tightly linked to spindle symmetry, correct microtubule-kinetochore attachment and chromosome segregation. Here we review mechanisms that regulate centrosome dynamics, with emphasis on the roles of key mitotic kinases in the proper timing of centrosome dynamics and how aberrancies in these processes may cause chromosomal instability and cancer.

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

Cited by 20 publications

References 71 publications

Separate to operate: control of centrosome positioning and separation

Separate to operate: control of centrosome positioning and separation

Mitotic Regulation by NEK Kinase Networks

Mitotic kinase cascades orchestrating timely disjunction and movement of centrosomes maintain chromosomal stability and prevent cancer

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