Mechanism of β-Adrenergic Receptor Desensitization in Cardiac Hypertrophy Is Increased β-Adrenergic Receptor Kinase [PDF]
Pressure overload cardiac hypertrophy in the mouse was achieved following 7 days of transverse aortic constriction. This was associated with marked beta-adrenergic receptor (beta-AR) desensitization in vivo, as determined by a blunted inotropic response to dobutamine. Extracts from hypertrophied hearts had approximately 3-fold increase in cytosolic and
D J, Choi +3 more
openaire +2 more sources
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis. [PDF]
The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-ε and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute
Ahmadian, Maryam +16 more
core +2 more sources
Inhibition of the beta-adrenergic receptor kinase by polyanions.
The beta-adrenergic receptor kinase, which specifically phosphorylates the agonist-occupied beta-adrenergic receptor, is strongly inhibited by polyanions. Heparin and dextran sulfate inhibit the enzyme with an IC50 of approximately 0.15 microM. De-N-sulfated heparin is approximately 8-fold less potent.
J L, Benovic +3 more
openaire +2 more sources
Purification and characterization of the beta-adrenergic receptor kinase.
The beta-adrenergic receptor kinase (beta-ARK) is a recently discovered enzyme which specifically phosphorylates the agonist-occupied form of the beta-adrenergic receptor (beta-AR) as well as the light-bleached form of rhodopsin. beta-ARK is present in a wide variety of mammalian tissues.
J L, Benovic +4 more
openaire +2 more sources
Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation [PDF]
β2-Adrenergic receptors (β2AR) transactivate epidermal growth factor receptors (EGFR) through formation of a β2AR-EGFR complex that requires activation of Src to mediate signaling. Here, we show that both lipid and protein kinase activities of the bifunctional phosphoinositide 3-kinase (PI3K) enzyme are required for β2AR-stimulated EGFR transactivation.
Lewis J, Watson +7 more
openaire +2 more sources
We tested the hypothesis that angiotensin II type 1 receptor blocker (ARB) may improve beta-adrenergic receptor (AR) coupling in heart failure (HF) after myocardial infarction (MI).Beta-AR desensitization is one of the mechanisms underlying the transition from compensated to decompensated HF.
Takahashi, Toshiyuki +7 more
openaire +2 more sources
Inhibition of beta-adrenergic receptor kinase prevents rapid homologous desensitization of beta 2-adrenergic receptors. [PDF]
Homologous (agonist-specific) desensitization of beta-adrenergic receptors (beta ARs) is accompanied by and appears to require phosphorylation of the receptors. We have recently described a novel protein kinase, beta AR kinase, which phosphorylates beta ARs in vitro in an agonist-dependent manner.
Lohse, MJ +3 more
openaire +2 more sources
This study explores nanoparticle delivery of the protein kinase C inhibitor bisindolylmaleimide‐I (BIM‐I) to combat influenza A virus infections. Encapsulation in biodegradable PLGA nanoparticles improved safety while maintaining the compound's strong antiviral activity.
Laura Klement +12 more
wiley +1 more source
Structure of the human gene encoding the beta-adrenergic receptor kinase.
The beta-adrenergic receptor kinase (beta ARK) specifically phosphorylates the agonist-occupied forms of the beta 2-adrenergic receptor and related G protein-coupled receptors. beta ARK is one of the best characterized members of a growing family of G protein-coupled receptor kinases.
R B, Penn, J L, Benovic
openaire +2 more sources
Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. [PDF]
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 in receptor phosphorylation remains largely unknown.
Benovic, JL +3 more
openaire +2 more sources

