Source:http://linkedlifedata.com/resource/pubmed/id/17200117
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2007-2-26
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pubmed:abstractText |
Gravin (AKAP12) is a membrane-associated scaffold that provides docking for protein kinases, phosphatases, and adaptor molecules obligate for resensitization and recycling of beta(2)-adrenergic receptors. Gravin binds to the cell membrane in a Ca(2+)-sensitive manner and to receptors through well characterized protein-protein interactions. Although the interaction of serine/threonine, cyclic AMP-dependent protein kinase with protein kinase A-anchoring proteins is well described and involves a kinase regulatory subunit binding domain in the C terminus of these proteins, far less is known about tyrosine kinase docking to members of this family of scaffolds. The non-receptor tyrosine kinase Src regulates resensitization of beta(2)-adrenergic receptors and docks to gravin. Gravin displays nine proline-rich domains distributed throughout the molecule. One class I ligand for Src homology domain 3 docking, found in the N terminus ((10)RXPXXP(15)) of gravin, is shown to bind Src. Binding of Src to gravin activates the intrinsic tyrosine kinase of Src. Mutagenesis/deletion of the class I ligand (P15A,P16A) on the N terminus of gravin abolishes both the docking of Src to gravin as well as the receptor resensitization and recycling catalyzed by gravin. The Src-binding peptide-(1-51) of gravin behaves as a dominant-negative for AKAP gravin regulation of receptor resensitization/recycling. The tyrosine kinase Src plays an essential role in the AKAP gravin-mediated receptor resensitization and recycling, an essential aspect of receptor biology.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/A Kinase Anchor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/AKAP12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6597-608
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17200117-A Kinase Anchor Proteins,
pubmed-meshheading:17200117-Cell Cycle Proteins,
pubmed-meshheading:17200117-Cell Line, Tumor,
pubmed-meshheading:17200117-Endocytosis,
pubmed-meshheading:17200117-Humans,
pubmed-meshheading:17200117-Mutagenesis,
pubmed-meshheading:17200117-Protein Binding,
pubmed-meshheading:17200117-Receptors, Adrenergic, beta-2,
pubmed-meshheading:17200117-src-Family Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
Src docks to A-kinase anchoring protein gravin, regulating beta2-adrenergic receptor resensitization and recycling.
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pubmed:affiliation |
Department of Pharmacology, State University of New York, Stony Brook, New York 11794-8651, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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