Publication Date:
2001-07-07
Description:
The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The beta(2) adrenergic receptor was found to be directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(v)1.2. This complex also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate-dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davare, M A -- Avdonin, V -- Hall, D D -- Peden, E M -- Burette, A -- Weinberg, R J -- Horne, M C -- Hoshi, T -- Hell, J W -- AG00213/AG/NIA NIH HHS/ -- AG17502/AG/NIA NIH HHS/ -- GM08688/GM/NIGMS NIH HHS/ -- GM56900/GM/NIGMS NIH HHS/ -- HL61645/HL/NHLBI NIH HHS/ -- NS35563/NS/NINDS NIH HHS/ -- NS39444/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Jul 6;293(5527):98-101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11441182" target="_blank"〉PubMed〈/a〉
Keywords:
Adenylyl Cyclases/metabolism
;
Adrenergic beta-2 Receptor Agonists
;
Albuterol/pharmacology
;
Animals
;
Calcium Channels, L-Type/genetics/*metabolism
;
Cell Line
;
Cell Membrane/metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Electric Conductivity
;
Fluorescent Antibody Technique
;
Heterotrimeric GTP-Binding Proteins/metabolism
;
Humans
;
Isoproterenol/pharmacology
;
Kinetics
;
Macromolecular Substances
;
Neurons/cytology/drug effects/enzymology/metabolism
;
Phosphoprotein Phosphatases/metabolism
;
Precipitin Tests
;
Prosencephalon/cytology/metabolism
;
Protein Binding
;
Pyramidal Cells/cytology/drug effects/enzymology/metabolism
;
Rats
;
Receptors, Adrenergic, beta-2/genetics/*metabolism
;
*Signal Transduction
;
Substrate Specificity
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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