Our goal is to identify molecular mechanisms involved in the regulation of the beta-adrenergic receptor (BAR)-coupled adenylyl cyclase. Although there are three subtypes, B1AR, B2AR and B3AR, the physiological relevance of each remains to be elucidated. One possibility is that they may be regulated differently by agonists and other modulators. At least three major mechanisms of receptor regulation have been identified: desensitization, internalization, and down-regulation. We and others have shown that for the human subtypes, the ability to undergo regulation is B2AR

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002366-20
Application #
6111834
Study Section
Special Emphasis Panel (LMCN)
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Rebois, R Victor; Maki, Karl; Meeks, Julie A et al. (2012) D2-like dopamine and ýý-adrenergic receptors form a signaling complex that integrates Gs- and Gi-mediated regulation of adenylyl cyclase. Cell Signal 24:2051-60
Liang, Wei; Fishman, Peter H (2004) Resistance of the human beta1-adrenergic receptor to agonist-induced ubiquitination: a mechanism for impaired receptor degradation. J Biol Chem 279:46882-9
Liang, Wei; Curran, Patricia K; Hoang, Quang et al. (2004) Differences in endosomal targeting of human (beta)1- and (beta)2-adrenergic receptors following clathrin-mediated endocytosis. J Cell Sci 117:723-34
Liang, Wei; Austin, Steven; Hoang, Quang et al. (2003) Resistance of the human beta 1-adrenergic receptor to agonist-mediated down-regulation. Role of the C terminus in determining beta-subtype degradation. J Biol Chem 278:39773-81
Fishman, Peter H; Orlandi, Palmer A (2003) Cholera toxin internalization and intoxication. J Cell Sci 116:431-2; author reply 432-3
Dunigan, Cheryl D; Hoang, Quang; Curran, Patricia K et al. (2002) Complexity of agonist- and cyclic AMP-mediated downregulation of the human beta 1-adrenergic receptor: role of internalization, degradation, and mRNA destabilization. Biochemistry 41:8019-30
Leavitt, M; Setola, V; Fishman, P H (2001) Protein kinase C-mediated down-regulation of beta(2)-adrenergic receptor and gene expression in rat C6 glioma cells. J Neurochem 77:823-9
Dunigan, C D; Curran, P K; Fishman, P H (2000) Detection of beta-adrenergic receptors by radioligand binding. Methods Mol Biol 126:329-43