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In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. 

Shah, AS; White, DC; Emani, S; Kypson, AP; Lilly, RE; Wilson, K; Glower, DD; ... (9 authors) (Circulation, 2001-03-06)
BACKGROUND: Genetic manipulation to reverse molecular abnormalities associated with dysfunctional myocardium may provide novel treatment. This study aimed to determine the feasibility and functional consequences of in vivo ...
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Augmentation of cardiac contractility mediated by the human beta(3)-adrenergic receptor overexpressed in the hearts of transgenic mice. 

Kohout, TA; Takaoka, H; McDonald, PH; Perry, SJ; Mao, L; Lefkowitz, RJ; Rockman, HA (Circulation, 2001-11-13)
BACKGROUND: Stimulation of beta(1)- and beta(2)-adrenergic receptors (ARs) in the heart results in positive inotropy. In contrast, it has been reported that the beta(3)AR is also expressed in the human heart and that its ...
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Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. 

Harding, VB; Jones, LR; Lefkowitz, RJ; Koch, WJ; Rockman, HA (Proc Natl Acad Sci U S A, 2001-05-08)
Chronic human heart failure is characterized by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased levels of betaAR kinase 1 (betaARK1), which seems critical to the pathogenesis of the disease. ...
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beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins. 

Chen, W; Hu, LA; Semenov, MV; Yanagawa, S; Kikuchi, A; Lefkowitz, RJ; Miller, WE (Proc Natl Acad Sci U S A, 2001-12-18)
One aspect of the function of the beta-arrestins is to serve as scaffold or adapter molecules coupling G-protein coupled receptors (GPCRs) to signal transduction pathways distinct from traditional second messenger pathways. ...
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Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. 

Freeman, K; Lerman, I; Kranias, EG; Bohlmeyer, T; Bristow, MR; Lefkowitz, RJ; Iaccarino, G; ... (9 authors) (J Clin Invest, 2001-04)
The medical treatment of chronic heart failure has undergone a dramatic transition in the past decade. Short-term approaches for altering hemodynamics have given way to long-term, reparative strategies, including beta-adrenergic ...
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Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. 

Luttrell, LM; Roudabush, FL; Choy, EW; Miller, WE; Field, ME; Pierce, KL; Lefkowitz, RJ (Proc Natl Acad Sci U S A, 2001-02-27)
Using both confocal immunofluorescence microscopy and biochemical approaches, we have examined the role of beta-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation ...
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beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking. 

Kohout, TA; Lin, FS; Perry, SJ; Conner, DA; Lefkowitz, RJ (Proc Natl Acad Sci U S A, 2001-02-13)
The two widely coexpressed isoforms of beta-arrestin (termed beta arrestin 1 and 2) are highly similar in amino acid sequence. The beta-arrestins bind phosphorylated heptahelical receptors to desensitize and target them ...
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Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes. 

Zhu, WZ; Zheng, M; Koch, WJ; Lefkowitz, RJ; Kobilka, BK; Xiao, RP (Proc Natl Acad Sci U S A, 2001-02-13)
The goal of this study was to determine whether beta(1)-adrenergic receptor (AR) and beta(2)-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One potential mechanism ...

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AuthorLefkowitz, RJ (8)Koch, WJ (4)Kohout, TA (2)Miller, WE (2)Perry, SJ (2)Rockman, HA (2)Bohlmeyer, T (1)Bristow, MR (1)Chen, W (1)Choy, EW (1)... View MoreDate Issued
2001 (8)
TypeJournal article (8)Subject
Animals (8)
Mice (6)Humans (4)Myocardium (4)Arrestins (3)beta-Adrenergic Receptor Kinases (3)beta-Arrestins (3)Cell Line (3)Cyclic AMP-Dependent Protein Kinases (3)Mice, Transgenic (3)... View MoreAffiliation of Duke Author(s)Basic Science Departments (8)Biochemistry (8)Chemistry (8)
Clinical Science Departments (8)
Duke (8)Duke Cancer Institute (8)
Institutes and Centers (8)
Medicine (8)
Medicine, Cardiology (8)Pathology (8)... View More
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