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Characterization of agonist stimulation of cAMP-dependent protein kinase and G protein-coupled receptor kinase phosphorylation of the beta2-adrenergic receptor using phosphoserine-specific antibodies.
- T. Tran, J. Friedman, Eyad A. Qunaibi, Faiza Baameur, Robert H. Moore, R. Clark
- Biology, ChemistryMolecular pharmacology
The results show a remarkable amplification of PKA site phosphorylation relative to the putative GRK siteosphorylation, heterologous stimulation of the PKASite phosphorylated, no dependence of GRK sites phosphorylations on PKA sites, and a reasonable correlation of initial levels ofGRK site phosphorlation with the strength of a range of agonists.
Localization of the sites mediating desensitization of the beta(2)-adrenergic receptor by the GRK pathway.
It is demonstrated that the cluster of serines within the 355 to 364 betaAR domain confer the rapid, GRK-mediated, receptor-level desensitization of the betaAR.
Identification of a specific site required for rapid heterologous desensitization of the beta-adrenergic receptor by cAMP-dependent protein kinase.
Results suggest that the action of cA.PK on amino acid residue(s) contained within the sequence 259-262 of the beta AR is required for rapid heterologous desensitization of the receptor in response to agonists.
Characterization of β2-Adrenergic Receptor Dephosphorylation: Comparison with the Rate of Resensitization
- T. Tran, J. Friedman, Faiza Baameur, B. Knoll, Robert H. Moore, R. Clark
- Biology, ChemistryMolecular Pharmacology
- 1 January 2007
Slow GRK site dephosphorylation after antagonist treatment was demonstrated by the relative stability of internalized phosphorylated β2AR in cells as observed both by immunofluorescence microscopy using a phospho-site-specific antibody and by studies of the subcellular localization of the GRK-phosphorlatedβ2AR on sucrose gradients that revealed nearly equivalent levels of GRK sites phosphorylation in the plasma membrane and vesicular fractions.
β2-Adrenergic Receptor Desensitization, Internalization, and Phosphorylation in Response to Full and Partial Agonists*
The data support the hypothesis that increasing agonist-coupling efficiency primarily affects desensitization by increasing the rate of βARK phosphorylation of the βAR and demonstrate an excellent proportionality between the agonist strength and agonists-induced desensItization, internalization, and the rapid initial phase of phosphorylated.
Identification and Cloning of Xp95, a Putative Signal Transduction Protein in Xenopus Oocytes*
The results suggest that Xp95 is an element in a tyrosine kinase signaling pathway that may be involved in progesterone-induced Xenopus oocyte maturation.
Roles of GRK and PDE4 Activities in the Regulation of β2 Adrenergic Signaling
- W. Xin, T. Tran, W. Richter, R. Clark, T. Rich
- Biology, ChemistryThe Journal of general physiology
- 1 April 2008
The data indicate that GRK-mediated desensitization is primarily responsible for a sustained suppression of β2AR signaling and PDE4 activity in controlling cAMP signals, and hence, on the overall sensitivity of the system.
Differential phosphorylation and dephosphorylation of β2‐adrenoceptor sites Ser262 and Ser355,356
- Varsha Iyer, T. Tran, Estrella A. Foster, W. Dai, R. Clark, B. Knoll
- Biology, ChemistryBritish Journal of Pharmacology
- 1 February 2006
The results indicate that the kinetics of β2‐adrenoceptor GRK and PKA site phosphorylation are distinct and differently affected by endocytosis, and that receptor dephosphorylation can occur either at the plasma membrane or in internal compartments.
Salmeterol stimulation dissociates beta2-adrenergic receptor phosphorylation and internalization.
- Robert H. Moore, E. Millman, R. Clark
- BiologyAmerican Journal of Respiratory Cell and…
- 1 February 2007
The data indicate that salmeterol binding induces an active receptor state that is unable to recruit beta-arrestin or undergo significant endocytosis or degradation despite stimulating considerable GRK-site phosphorylation.
Accelerated dephosphorylation of the beta2-adrenergic receptor by mutation of the C-terminal lysines: effects on ubiquitination, intracellular trafficking, and degradation.
It is indicated that both phosphorylation and ubiquitination are involved in the intracellular sorting of beta 2AR between pathways of recycling to the plasma membrane and degradation in lysosomes, and that the rate of dephosphorylation may be another mechanism of regulating the sorting.