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Browsing by Author "Lefkowitz, RJ"
Now showing items 1-20 of 76
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A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination.
(Proc Natl Acad Sci U S A, 1993-02-15)We have previously shown that second-messenger-dependent kinases (cAMP-dependent kinase, protein kinase C) in the olfactory system are essential in terminating second-messenger signaling in response to odorants. We now document ... -
A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins.
(Proc Natl Acad Sci U S A, 1998-07-21)The Na+/H+ exchanger regulatory factor (NHERF) binds to the tail of the beta2-adrenergic receptor and plays a role in adrenergic regulation of Na+/H+ exchange. NHERF contains two PDZ domains, the first of which is required ... -
A constitutively active mutant beta 2-adrenergic receptor is constitutively desensitized and phosphorylated.
(Proc Natl Acad Sci U S A, 1994-03-29)The beta 2-adrenergic receptor (beta 2AR) can be constitutively activated by mutations in the third intracellular loop. Whereas the wild-type receptor exists predominantly in an inactive conformation (R) in the absence of ... -
Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds.
(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 ... -
Adrenergic receptors. Models for regulation of signal transduction processes.
(Hypertension, 1990-02)Adrenergic receptors are prototypic models for the study of the relations between structure and function of G protein-coupled receptors. Each receptor is encoded by a distinct gene. These receptors are integral membrane ... -
Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy.
(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 ... -
An approach to the study of G-protein-coupled receptor kinases: an in vitro-purified membrane assay reveals differential receptor specificity and regulation by G beta gamma subunits.
(Proc Natl Acad Sci U S A, 1994-04-26)Phosphorylation of GTP-binding-regulatory (G)-protein-coupled receptors by specific G-protein-coupled receptor kinases (GRKs) is a major mechanism responsible for agonist-mediated desensitization of signal transduction processes. ... -
Augmentation of cardiac contractility mediated by the human beta(3)-adrenergic receptor overexpressed in the hearts of transgenic mice.
(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-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor.
(Proc Natl Acad Sci U S A, 1986-05)Agonist-promoted desensitization of adenylate cyclase is intimately associated with phosphorylation of the beta-adrenergic receptor in mammalian, avian, and amphibian cells. However, the nature of the protein kinase(s) involved ... -
Beta-agonist- and prostaglandin E1-induced translocation of the beta-adrenergic receptor kinase: evidence that the kinase may act on multiple adenylate cyclase-coupled receptors.
(Proc Natl Acad Sci U S A, 1986-09)beta-Adrenergic receptor kinase (beta-AR kinase) is a cytosolic enzyme that phosphorylates the beta-adrenergic receptor only when it is occupied by an agonist [Benovic, J. Strasser, R. H., Caron, M. G. & Lefkowitz, R. J. ... -
beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking.
(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.
(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. ... -
beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein.
(Proc Natl Acad Sci U S A, 1998-11-24)G protein-coupled receptor activation leads to the membrane recruitment and activation of G protein-coupled receptor kinases, which phosphorylate receptors and lead to their inactivation. We have identified a novel ... -
cAMP stimulates transcription of the beta 2-adrenergic receptor gene in response to short-term agonist exposure.
(Proc Natl Acad Sci U S A, 1989-07)In addition to conveying cellular responses to an effector molecule, receptors are often themselves regulated by their effectors. We have demonstrated that epinephrine modulates both the rate of transcription of the beta ... -
Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure.
(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. ... -
Catecholamines, cardiac beta-adrenergic receptors, and heart failure.
(Circulation, 2000-04-11) -
cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor.
(Proc Natl Acad Sci U S A, 1987-01)We have isolated and sequenced a cDNA encoding the human beta 2-adrenergic receptor. The deduced amino acid sequence (413 residues) is that of a protein containing seven clusters of hydrophobic amino acids suggestive of ... -
Chromosomal organization of adrenergic receptor genes.
(Proc Natl Acad Sci U S A, 1990-02)The adrenergic receptors (ARs) (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone ... -
Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype.
(Proc Natl Acad Sci U S A, 1988-09)An alpha 2-adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet alpha 2-adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet ... -
Cloning of the cDNA for the human beta 1-adrenergic receptor.
(Proc Natl Acad Sci U S A, 1987-11)Screening of a human placenta lambda gt11 library has led to the isolation of the cDNA for the human beta 1-adrenergic receptor (beta 1AR). Used as the probe was the human genomic clone termed G-21. This clone, which contains ...
