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

    Emani, S; Glower, Donald D Jr; Koch, Walter J; Kypson, Alan P; Lefkowitz, Robert J; Lilly, R Eric; Shah, AS; ... (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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    beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. 

    Baillie, GS; Gall, I; Houslay, MD; Lefkowitz, Robert J; McPhee, I; Perry, SJ; Sood, A (Proc Natl Acad Sci U S A, 2003-02-04)
    Phosphorylation of the beta(2) adrenoreceptor (beta(2)AR) by cAMP-activated protein kinase A (PKA) switches its predominant coupling from stimulatory guanine nucleotide regulatory protein (G(s)) to inhibitory guanine nucleotide ...
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    Hybrid transgenic mice reveal in vivo specificity of G protein-coupled receptor kinases in the heart. 

    Benovic, JL; Duncan, SJ; Eckhart, AD; Koch, Walter J; Lefkowitz, Robert J; Penn, RB (Circ Res, 2000-01-07)
    G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors, including alpha(1B)-adrenergic receptors (ARs), resulting in desensitization. In vivo analysis of GRK substrate selectivity has ...
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    Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. 

    Bohlmeyer, T; Bristow, MR; Freeman, K; Iaccarino, Guido; Koch, Walter J; Kranias, EG; Lefkowitz, Robert J; ... (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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    Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. 

    Glower, Donald D Jr; Hata, Jonathan Andrew; Koch, Walter J; Lefkowitz, Robert J; Shah, AS; White, DC (Proc Natl Acad Sci U S A, 2000-05-09)
    When the heart fails, there is often a constellation of biochemical alterations of the beta-adrenergic receptor (betaAR) signaling system, leading to the loss of cardiac inotropic reserve. betaAR down-regulation and functional ...
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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; Koch, Walter J; Lefkowitz, Robert J; Rockman, Howard A (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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    The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels. 

    Cook, DI; Dinudom, A; Fotia, AB; Kumar, S; Lefkowitz, Robert J; Young, JA (Proc Natl Acad Sci U S A, 2004-08-10)
    Epithelial Na(+) channels mediate the transport of Na across epithelia in the kidney, gut, and lungs and are required for blood pressure regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, ...
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    Level of beta-adrenergic receptor kinase 1 inhibition determines degree of cardiac dysfunction after chronic pressure overload-induced heart failure. 

    Koch, Walter J; Lefkowitz, Robert J; Naga Prasad, SV; Rockman, Howard A; Tachibana, H (Circulation, 2005-02-08)
    BACKGROUND: Heart failure is characterized by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased level of myocardial betaAR kinase 1 (betaARK1). Our previous studies have shown that inhibition ...
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    Purification, crystallization and preliminary X-ray diffraction studies of a complex between G protein-coupled receptor kinase 2 and Gbeta1gamma2. 

    Barnhill, JF; Capel, WD; Lefkowitz, Robert J; Lodowski, DT; Pitcher, JA; Tesmer, JJG (Acta Crystallogr D Biol Crystallogr, 2003-05)
    G protein-coupled receptor kinase 2 (GRK2) phosphorylates activated G protein-coupled receptors (GPCRs), which ultimately leads to their desensitization and/or downregulation. The enzyme is recruited to the plasma membrane ...
     

     

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    Lefkowitz, Robert J (9)
    Koch, Walter J (6)Glower, Donald D Jr (2)Rockman, Howard A (2)Shah, AS (2)White, DC (2)Baillie, GS (1)Barnhill, JF (1)Benovic, JL (1)Bohlmeyer, T (1)... View MoreDate Issued2001 (3)2000 (2)2003 (2)2004 (1)2005 (1)TypeJournal article (9)SubjectAnimals (9)
    Cyclic AMP-Dependent Protein Kinases (9)
    beta-Adrenergic Receptor Kinases (8)Myocardium (6)Mice (5)Male (4)Mice, Transgenic (4)Cell Line (3)Gene Expression (3)Signal Transduction (3)... View MoreAffiliation of Duke Author(s)Basic Science Departments (9)Biochemistry (9)Chemistry (9)
    Clinical Science Departments (9)
    Duke (9)Duke Cancer Institute (9)Institutes and Centers (9)
    Medicine (9)
    Medicine, Cardiology (9)Pathology (9)... View More