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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; Lefkowitz, Robert J; Mao, L; McDonald, Patricia H; Perry, SJ; Rockman, Howard A; Takaoka, H (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 ...

beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.

Chen, JR; DeWire, SM; Kovacs, JJ; Lam, CM; Lefkowitz, Robert J; Muehlbauer, Michael J; Shukla, Arun Kumar; ... (10 authors) (J Clin Invest, 2009-05)

Nicotinic acid is one of the most effective agents for both lowering triglycerides and raising HDL. However, the side effect of cutaneous flushing severely limits patient compliance. As nicotinic acid stimulates the GPCR ...

Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.

Barki-Harrington, L; Chen, J; Le Corvoisier, P; Lefkowitz, Robert J; Lemaire, A; Naga Prasad, SV; Noma, T; ... (11 authors) (J Clin Invest, 2007-09)

Deleterious effects on the heart from chronic stimulation of beta-adrenergic receptors (betaARs), members of the 7 transmembrane receptor family, have classically been shown to result from Gs-dependent adenylyl ...

Smoothened signal transduction is promoted by G protein-coupled receptor kinase 2.

Caron, MG; Chen, JK; Fralish, GB; Kelly, P; Lefkowitz, Robert J; Meloni, AR; Salahpour, A; ... (8 authors) (Mol Cell Biol, 2006-10)

Deregulation of the Sonic hedgehog pathway has been implicated in an increasing number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation ...

beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking.

Conner, DA; Kohout, TA; Lefkowitz, Robert J; Lin, FS; Perry, SJ (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 ...

beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins.

Chen, W; Hu, LA; Kikuchi, A; Lefkowitz, Robert J; Miller, WE; Semenov, MV; Yanagawa, S (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. ...

Intracoronary adenovirus-mediated delivery and overexpression of the beta(2)-adrenergic receptor in the heart : prospects for molecular ventricular assistance.

Glower, Donald D Jr; Hata, Jonathan Andrew; Koch, Walter J; Kypson, Alan P; Lefkowitz, Robert J; Lilly, R Eric; Pippen, Anne; ... (10 authors) (Circulation, 2000-02-01)

BACKGROUND: Genetic modulation of ventricular function may offer a novel therapeutic strategy for patients with congestive heart failure. Myocardial overexpression of beta(2)-adrenergic receptors (beta(2)ARs) has been shown ...