| pubmed-article:15653687 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15653687 | lifeskim:mentions | umls-concept:C0682972 | lld:lifeskim |
| pubmed-article:15653687 | lifeskim:mentions | umls-concept:C0031727 | lld:lifeskim |
| pubmed-article:15653687 | lifeskim:mentions | umls-concept:C0542341 | lld:lifeskim |
| pubmed-article:15653687 | lifeskim:mentions | umls-concept:C1372999 | lld:lifeskim |
| pubmed-article:15653687 | lifeskim:mentions | umls-concept:C0678594 | lld:lifeskim |
| pubmed-article:15653687 | lifeskim:mentions | umls-concept:C0936012 | lld:lifeskim |
| pubmed-article:15653687 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:15653687 | pubmed:dateCreated | 2005-3-21 | lld:pubmed |
| pubmed-article:15653687 | pubmed:abstractText | G protein-coupled receptors (GPCRs) mediate the ability of a diverse array of extracellular stimuli to control intracellular signaling. Many GPCRs are phosphorylated by G protein-coupled receptor kinases (GRKs), a process that mediates agonist-specific desensitization in many cells. Although GRK binding to activated GPCRs results in kinase activation and receptor phosphorylation, relatively little is known about the mechanism of GRK/GPCR interaction or how this interaction results in kinase activation. Here, we used the alpha2A-adrenergic receptor (alpha(2A)AR) as a model to study GRK/receptor interaction because GRK2 phosphorylation of four adjacent serines within the large third intracellular loop of this receptor is known to mediate desensitization. Various domains of the alpha(2A)AR were expressed as glutathione S-transferase fusion proteins and tested for the ability to bind purified GRK2. The second and third intracellular loops of the alpha(2A)AR directly interacted with GRK2, whereas the first intracellular loop and C-terminal domain did not. Truncation mutagenesis identified three discrete regions within the third loop that contributed to GRK2 binding, the membrane proximal N- and C-terminal regions as well as a central region adjacent to the phosphorylation sites. Site-directed mutagenesis revealed a critical role for specific basic residues within these regions in mediating GRK2 interaction with the alpha(2A)AR. Mutation of these residues within the holo-alpha(2A)AR diminished GRK2-promoted phosphorylation of the receptor as well as the ability of the kinase to be activated by receptor binding. These studies provide new insight into the mechanism of interaction and activation of GRK2 by GPCRs and suggest that GRK2 binding is critical not only for receptor phosphorylation but also for full activity of the kinase. | lld:pubmed |
| pubmed-article:15653687 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15653687 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15653687 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15653687 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15653687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15653687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15653687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15653687 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15653687 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:15653687 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:15653687 | pubmed:author | pubmed-author:BenovicJeffre... | lld:pubmed |
| pubmed-article:15653687 | pubmed:author | pubmed-author:PaoChristina... | lld:pubmed |
| pubmed-article:15653687 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15653687 | pubmed:day | 25 | lld:pubmed |
| pubmed-article:15653687 | pubmed:volume | 280 | lld:pubmed |
| pubmed-article:15653687 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15653687 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15653687 | pubmed:pagination | 11052-8 | lld:pubmed |
| pubmed-article:15653687 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
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| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:meshHeading | pubmed-meshheading:15653687... | lld:pubmed |
| pubmed-article:15653687 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15653687 | pubmed:articleTitle | Structure/function analysis of alpha2A-adrenergic receptor interaction with G protein-coupled receptor kinase 2. | lld:pubmed |
| pubmed-article:15653687 | pubmed:affiliation | Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. | lld:pubmed |
| pubmed-article:15653687 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15653687 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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