Source:http://linkedlifedata.com/resource/pubmed/id/15271984
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
40
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| pubmed:dateCreated |
2004-9-27
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| pubmed:abstractText |
G protein-coupled receptor kinase-2 (GRK2) can phosphorylate and desensitize the platelet-derived growth factor receptor-beta (PDGFRbeta) in heterologous cellular systems. To determine whether GRK2 regulates the PDGFRbeta in physiologic systems, we examined PDGFRbeta signaling in mouse embryonic fibroblasts from GRK2-null and cognate wild type mice. To discern a mechanism by which GRK2-mediated phosphorylation can desensitize the PDGFRbeta, but not the epidermal growth factor receptor (EGFR), we investigated effects of GRK2-mediated phosphorylation on the association of the PDGFRbeta with the Na(+)/H(+) exchanger regulatory factor (NHERF), a protein shown to potentiate dimerization of the PDGFRbeta, but not the EGFR. Physiologic expression of GRK2 diminished (a) phosphoinositide hydrolysis elicited through the PDGFRbeta but not heterotrimeric G proteins; (b) Akt activation evoked by the PDGFRbeta but not the EGFR; and (c) PDGF-induced tyrosyl phosphorylation of the PDGFRbeta itself. PDGFRbeta desensitization by physiologically expressed GRK2 correlated with a 2.5-fold increase in PDGF-promoted PDGFRbeta seryl phosphorylation. In 293 cells, GRK2 overexpression reduced PDGFRbeta/NHERF association by 60%. This effect was reproduced by S1104D mutation of the PDGFRbeta, which also diminished PDGFRbeta activation and signaling (like the S1104A mutation) to an extent equivalent to that achieved by GRK2-mediated PDGFRbeta phosphorylation. GRK2 overexpression desensitized only the wild type but not the S1104A PDGFRbeta. We conclude that GRK2-mediated PDGFRbeta seryl phosphorylation plays an important role in desensitizing the PDGFRbeta in physiologic systems. Furthermore, this desensitization appears to involve GRK2-mediated phosphorylation of PDGFRbeta Ser(1104), with consequent dissociation of the PDGFRbeta from NHERF.
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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/ADRBK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Adrbk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Hydrogen Antiporter,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Adrenergic Receptor Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/sodium-hydrogen exchanger...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
279
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
41775-82
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15271984-Animals,
pubmed-meshheading:15271984-Cattle,
pubmed-meshheading:15271984-Cell Line,
pubmed-meshheading:15271984-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:15271984-Epidermal Growth Factor,
pubmed-meshheading:15271984-Fibroblasts,
pubmed-meshheading:15271984-G-Protein-Coupled Receptor Kinase 3,
pubmed-meshheading:15271984-Humans,
pubmed-meshheading:15271984-Mice,
pubmed-meshheading:15271984-Phosphoproteins,
pubmed-meshheading:15271984-Phosphorylation,
pubmed-meshheading:15271984-Protein Binding,
pubmed-meshheading:15271984-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:15271984-Serine,
pubmed-meshheading:15271984-Signal Transduction,
pubmed-meshheading:15271984-Sodium-Hydrogen Antiporter,
pubmed-meshheading:15271984-Transfection,
pubmed-meshheading:15271984-beta-Adrenergic Receptor Kinases
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| pubmed:year |
2004
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| pubmed:articleTitle |
Phosphorylation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na(+)/H(+) exchanger regulatory factor.
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| pubmed:affiliation |
Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina 27710, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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