{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:57:30Z","timestamp":1767833850302,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,3,12]],"date-time":"2007-03-12T00:00:00Z","timestamp":1173657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>G protein\u2010coupled receptor kinase 2 (GRK2) modulates G protein\u2010coupled receptor desensitization and signaling. We previously described down\u2010regulation of GRK2 expression <jats:italic>in\u00a0vivo<\/jats:italic> in rat neonatal brain following hypoxia\u2010ischemia. In this study, we investigated the molecular mechanisms involved in GRK2 down\u2010regulation, using organotypic cultures of neonatal rat hippocampal slices exposed to oxygen and glucose deprivation (OGD). We observed a 40% decrease in GRK2 expression 4\u2003h post\u2010OGD. No changes in GRK2 protein occurred after exposure of hippocampal slices to glucose deprivation only. No significant alterations in GRK2 mRNA expression were detected, suggesting a post\u2010transcriptional effect of OGD on GRK2 expression. Blockade of the proteasome pathway by MG132 prevented OGD\u2010induced decrease of GRK2. It has been shown that extracellular signal\u2010regulated kinase\u2010dependent phosphorylation of GRK2 at Ser670 triggers its turnover via the proteasome pathway. However, despite a significant increase of pSer670\u2010GRK2 after OGD, inhibition of the extracellular signal\u2010regulated kinase pathway by PD98059 did neither prevent the hypoxia\u2010ischemia\u2010induced increase in pSer670\u2010GRK2 nor the down\u2010regulation of GRK2 protein. Interestingly, inhibition of phosphoinositide\u20103\u2010kinase with wortmannin inhibits both OGD\u2010induced phosphorylation of GRK2 on Ser670 and the GRK2 decrease. In conclusion, OGD\u2010induced phosphoinositide\u20103\u2010kinase\u2010dependent phosphorylation of GRK2 on Ser670 is a novel mechanism leading to down\u2010regulation of GRK2 protein via a proteasome\u2010dependent pathway.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04576.x","type":"journal-article","created":{"date-parts":[[2007,5,2]],"date-time":"2007-05-02T15:41:10Z","timestamp":1178120470000},"page":"731-740","source":"Crossref","is-referenced-by-count":14,"title":["Down\u2010regulation of GRK2 after oxygen and glucose deprivation in rat hippocampal slices: role of the PI3\u2010kinase pathway"],"prefix":"10.1111","volume":"102","author":[{"given":"Maria Stella","family":"Lombardi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Vroon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Sodaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Freek L.","family":"Van Muiswinkel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cobi J.","family":"Heijnen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemieke","family":"Kavelaars","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,3,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1523\/JNEUROSCI.12-10-04045.1992","article-title":"The G\u2010protein\u2010coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain","volume":"12","author":"Arriza J. 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