Source:http://linkedlifedata.com/resource/pubmed/id/17442679
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
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| pubmed:dateCreated |
2007-6-11
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| pubmed:abstractText |
Phosphorylation can affect both the function and trafficking of GABA(A) receptors with significant consequences for neuronal excitability. Serine/threonine kinases can phosphorylate the intracellular loops between M3-4 of GABA(A) receptor beta and gamma subunits thereby modulating receptor function in heterologous expression systems and in neurons (1, 2). Specifically, CaMK-II has been demonstrated to phosphorylate the M3-4 loop of GABA(A) receptor subunits expressed as GST fusion proteins (3, 4). It also increases the amplitude of GABA(A) receptor-mediated currents in a number of neuronal cell types (5-7). To identify which substrate sites CaMK-II might phosphorylate and the consequent functional effects, we expressed recombinant GABA(A) receptors in NG108-15 cells, which have previously been shown to support CaMK-II modulation of GABA(A) receptors containing the beta3 subunit (8). We now demonstrate that CaMK-II mediates its effects on alpha1beta3 receptors via phosphorylation of Ser(383) within the M3-4 domain of the beta subunit. Ablation of beta3 subunit phosphorylation sites for CaMK-II revealed that for alphabetagamma receptors, CaMK-II has a residual effect on GABA currents that is not mediated by previously identified sites of CaMK-II phosphorylation. This residual effect is abolished by mutation of tyrosine phosphorylation sites, Tyr(365) and Tyr(367), on the gamma2S subunit, and by the tyrosine kinase inhibitor genistein. These results suggested that CaMK-II is capable of directly phosphorylating GABA(A) receptors and activating endogenous tyrosine kinases to phosphorylate the gamma2 subunit in NG108-15 cells. These findings were confirmed in a neuronal environment by expressing recombinant GABA(A) receptors in cerebellar granule neurons.
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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/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/GABRA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GABRB3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GABRG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gabra1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Gabrb3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Gabrg2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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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 |
17855-65
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:17442679-Animals,
pubmed-meshheading:17442679-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:17442679-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:17442679-Cells, Cultured,
pubmed-meshheading:17442679-Cerebellum,
pubmed-meshheading:17442679-Enzyme Activation,
pubmed-meshheading:17442679-Humans,
pubmed-meshheading:17442679-Mice,
pubmed-meshheading:17442679-Patch-Clamp Techniques,
pubmed-meshheading:17442679-Phosphorylation,
pubmed-meshheading:17442679-Protein Subunits,
pubmed-meshheading:17442679-Protein-Tyrosine Kinases,
pubmed-meshheading:17442679-Rats,
pubmed-meshheading:17442679-Rats, Sprague-Dawley,
pubmed-meshheading:17442679-Receptors, GABA-A,
pubmed-meshheading:17442679-Recombinant Fusion Proteins,
pubmed-meshheading:17442679-Serine,
pubmed-meshheading:17442679-Tyrosine
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| pubmed:year |
2007
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| pubmed:articleTitle |
Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors.
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| pubmed:affiliation |
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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