2004
DOI: 10.1128/mcb.24.23.10169-10179.2004
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G Protein-Coupled Receptor Kinase 5 Contains a DNA-Binding Nuclear Localization Sequence

Abstract: G protein-coupled receptor kinases (GRKs) mediate desensitization of agonist-occupied G protein-coupled receptors (GPCRs). Here we report that GRK5 contains a DNA-binding nuclear localization sequence (NLS) and that its nuclear localization is regulated by GPCR activation, results that suggest potential nuclear functions for GRK5. As assessed by fluorescence confocal microscopy, transfected and endogenous GRK5 is present in the nuclei of HEp2 cells. Mutation of basic residues in the catalytic domain of GRK5 (b… Show more

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Cited by 110 publications
(123 citation statements)
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References 42 publications
(47 reference statements)
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“…Moreover, the nuclear accumulation of GRK5 in myocytes was in direct result to Gq activation (5). Interestingly, PKC activation by PMA has also been shown to induce GRK5 nuclear localization (4,6).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Moreover, the nuclear accumulation of GRK5 in myocytes was in direct result to Gq activation (5). Interestingly, PKC activation by PMA has also been shown to induce GRK5 nuclear localization (4,6).…”
Section: Discussionmentioning
confidence: 99%
“…G protein-coupled receptors (GPCRs) 4 , such as ␤-adrenergic receptors (␤ARs), play crucial signaling and functional roles in the heart. GPCRs undergo nodal regulation following agonist activation triggered by phosphorylation via family of kinases such as GPCR kinases (GRKs) (1,2).…”
mentioning
confidence: 99%
“…GRK5 is unique compared with GRK2 as it has a functional nuclear localization signal (NLS) (9), and indeed, it has been found in the nucleus of myocytes (6,8,10,11). In fact, nuclear localization has been shown to be the determinant of cardiomyopathy after pressure overload where it has non-GPCR activity as a class II histone deacetylase kinase driving cardiac hypertrophic gene transcription (8,12).…”
mentioning
confidence: 99%
“…The catalytic domain of GRKs is relatively well-conserved among the members of different subfamilies (Ϸ45% sequence identity), whereas N-terminal RH domains display weak homology (Ϸ27%) and C termini have little or no sequence homology. GRKs have different tissue distribution, subcellular localization, and kinase activity regulation (7,8). GRKs mostly localize at the plasma membrane (2), but recently Johnson et al (7) demonstrated that GRK4-6 (but not other GRKs) can shuttle between cytosol and nucleus through functional nuclear localization sequence (NLS) and nuclear exporting sequence (NES), thus suggesting a nuclear effect for the GRK4-6 subfamily.…”
mentioning
confidence: 99%