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Role of G protein-c...
Role of G protein-coupled receptor kinases (GRKs) in β2-adrenoceptor-mediated glucose uptake
- Article/chapterEnglish2024
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LIBRIS-ID:oai:DiVA.org:su-226949
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-226949URI
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https://doi.org/10.1002/prp2.1176DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Truncation of the C-terminal tail of the beta(2)-AR, transfection of beta ARKct or over-expression of a kinase-dead GRK mutant reduces isoprenaline-stimulated glucose uptake, indicating that GRK is important for this response. We explored whether phosphorylation of the beta(2)-AR by GRK2 has a role in glucose uptake or if this response is related to the role of GRK2 as a scaffolding protein. CHO-GLUT4myc cells expressing wild-type and mutant beta(2)-ARs were generated and receptor affinity for [H-3]-CGP12177A and density of binding sites determined together with the affinity of isoprenaline and BRL37344. Following receptor activation by beta(2)-AR agonists, cAMP accumulation, GLUT4 translocation, [H-3]-2-deoxyglucose uptake, and beta(2)-AR internalization were measured. Bioluminescence resonance energy transfer was used to investigate interactions between beta(2)-AR and beta-arrestin2 or between beta(2)-AR and GRK2. Glucose uptake after siRNA knockdown or GRK inhibitors was measured in response to beta(2)-AR agonists. BRL37344 was a poor partial agonist for cAMP generation but displayed similar potency and efficacy to isoprenaline for glucose uptake and GLUT4 translocation. These responses to beta(2)-AR agonists occurred in CHO-GLUT4myc cells expressing beta(2)-ARs lacking GRK or GRK/PKA phosphorylation sites as well as in cells expressing the wild-type beta(2)-AR. However, beta(2)-ARs lacking phosphorylation sites failed to recruit beta-arrestin2 and did not internalize. GRK2 knock-down or GRK2 inhibitors decreased isoprenaline-stimulated glucose uptake in rat L6 skeletal muscle cells. Thus, GRK phosphorylation of the beta(2)-AR is not associated with isoprenaline- or BRL37344-stimulated glucose uptake. However, GRKs acting as scaffold proteins are important for glucose uptake as GRK2 knock-down or GRK2 inhibition reduces isoprenaline-stimulated glucose uptake.
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Mukaida, Saori
(author)
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Sato, Masaaki
(author)
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Keov, Peter
(author)
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Bengtsson, Tore,1970-Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)tbeng
(author)
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Furness, Sebastian
(author)
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Holliday, Nicholas D.
(author)
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Evans, Bronwyn A.
(author)
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Summers, Roger J.
(author)
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Hutchinson, Dana S.
(author)
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Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut
(creator_code:org_t)
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In:Pharmacology Research & Perspectives12:12052-1707
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Ham, Seungmin
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Mukaida, Saori
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Sato, Masaaki
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Keov, Peter
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Bengtsson, Tore, ...
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Furness, Sebasti ...
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Holliday, Nichol ...
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Evans, Bronwyn A ...
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Summers, Roger J ...
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Hutchinson, Dana ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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Pharmacology Res ...
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Stockholm University