期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 60
卷 60, 期 -, 页码 155-174出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010919-023404
关键词
G(s); adenylyl cyclase; PSD-95; AKAP; cAMP; norepinephrine
资金
- NIH [R01HL098200, R01HL121059, R01NS078792, R01MH097887, R01AG055357]
Formation of signaling complexes is crucial for the orchestration of fast, efficient, and specific signal transduction. Pharmacological disruption of defined signaling complexes has the potential for specific intervention in selected regulatory pathways without affecting organism-wide disruption of parallel pathways. Signaling by epinephrine and norepinephrine through cy and beta adrenergic receptors acts on many signaling pathways in many cell types. Here, we initially provide an overview of the signaling complexes formed between the paradigmatic beta(2) adrenergic receptor and two of its most important targets, the L-type Ca2+ channel Ca(V)1.2 and the AMPA-type glutamate receptor. Importantly, both complexes contain the trimeric G(s) protein, adenylyl cyclase, and the cAMP-dependent protein kinase, PKA. We then discuss the functional implications of the formation of these complexes, how those complexes can be specifically disrupted, and how such disruption could be utilized in the pharmacological treatment of disease.
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