| pubmed-article:12446706 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C0026336 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C2698694 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C0265341 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C0000936 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C0086376 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C1428114 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:12446706 | lifeskim:mentions | umls-concept:C1704735 | lld:lifeskim |
| pubmed-article:12446706 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:12446706 | pubmed:dateCreated | 2003-2-24 | lld:pubmed |
| pubmed-article:12446706 | pubmed:abstractText | Regulators of G protein signaling (RGS) are GTPase-accelerating proteins (GAPs), which can inhibit heterotrimeric G protein pathways. In this study, we provide experimental and theoretical evidence that high concentrations of receptors (as at a synapse) can lead to saturation of GDP-GTP exchange making GTP hydrolysis rate-limiting. This results in local depletion of inactive heterotrimeric G-GDP, which is reversed by RGS GAP activity. Thus, RGS enhances receptor-mediated G protein activation even as it deactivates the G protein. Evidence supporting this model includes a GTP-dependent enhancement of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding to G(i) by RGS. The RGS domain of RGS4 is sufficient for this, not requiring the NH(2)- or COOH-terminal extensions. Furthermore, a kinetic model including only the GAP activity of RGS replicates the GTP-dependent enhancement of GTPgammaS binding observed experimentally. Finally in a Monte Carlo model, this mechanism results in a dramatic "spatial focusing" of active G protein. Near the receptor, G protein activity is maintained even with RGS due to the ability of RGS to reduce depletion of local Galpha-GDP levels permitting rapid recoupling to receptor and maintained G protein activation near the receptor. In contrast, distant signals are suppressed by the RGS, since Galpha-GDP is not depleted there. Thus, a novel RGS-mediated "kinetic scaffolding" mechanism is proposed which narrows the spatial range of active G protein around a cluster of receptors limiting the spill-over of G protein signals to more distant effector molecules, thus enhancing the specificity of G(i) protein signals. | lld:pubmed |
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| pubmed-article:12446706 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:12446706 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12446706 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12446706 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12446706 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:12446706 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:12446706 | pubmed:author | pubmed-author:TraynorJohn... | lld:pubmed |
| pubmed-article:12446706 | pubmed:author | pubmed-author:NeubigRichard... | lld:pubmed |
| pubmed-article:12446706 | pubmed:author | pubmed-author:ZhongHuailing... | lld:pubmed |
| pubmed-article:12446706 | pubmed:author | pubmed-author:LindermanJenn... | lld:pubmed |
| pubmed-article:12446706 | pubmed:author | pubmed-author:WadeSusan MSM | lld:pubmed |
| pubmed-article:12446706 | pubmed:author | pubmed-author:WoolfPeter... | lld:pubmed |
| pubmed-article:12446706 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12446706 | pubmed:day | 28 | lld:pubmed |
| pubmed-article:12446706 | pubmed:volume | 278 | lld:pubmed |
| pubmed-article:12446706 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12446706 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12446706 | pubmed:pagination | 7278-84 | lld:pubmed |
| pubmed-article:12446706 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:12446706 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12446706 | pubmed:articleTitle | A spatial focusing model for G protein signals. Regulator of G protein signaling (RGS) protien-mediated kinetic scaffolding. | lld:pubmed |
| pubmed-article:12446706 | pubmed:affiliation | Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109-0632, USA. | lld:pubmed |
| pubmed-article:12446706 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12446706 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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