Robin Pals-Rylaarsdam

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The rapid decrease of a response to a persistent stimulus, often termed desensitization, is a widespread biological phenomenon. Signal transduction by numerous G protein-coupled receptors appears to be terminated by a strikingly uniform two-step mechanism, most extensively characterized for the beta2-adrenergic receptor (beta2AR), m2 muscarinic cholinergic(More)
The phenomenon of acute desensitization of G-protein-coupled receptors has been associated with several events, including receptor phosphorylation, loss of high affinity agonist binding, receptor:G-protein uncoupling, and receptor internalization. However, the biochemical events underlying these processes are not fully understood, and their contributions to(More)
To understand what processes contribute to the agonist-induced internalization of subtypes of muscarinic acetylcholine receptors, we analyzed the role of arrestins. Whereas the m2 mAChR has been shown to undergo augmented internalization when arrestins 2 and 3 are overexpressed (Pals-Rylaarsdam, R., Gurevich, V. V., Lee, K. B., Ptasienski, J. A., Benovic,(More)
Recent studies have identified agonist-dependent phosphorylation as a critical event in the rapid uncoupling of the m2 muscarinic cholinergic receptors (mAChR) from G-proteins and sequestration of the receptors away from the cell surface. However, mutant m2 mAChRs were identified that were phosphorylated but unable to desensitize in adenylyl cyclase assays,(More)
Short term exposure of m2 muscarinic acetylcholine receptors (m2 mAChRs) to agonist causes a rapid phosphorylation of the activated receptors, followed by a profound loss in the ability of the m2 mAChR to activate its signaling pathways. We have used site-directed mutagenesis to identify two clusters of Ser/Thr residues in the third intracellular loop of(More)
Desensitization of G protein-coupled receptors (GPCRs) involves the binding of members of the family of arrestins to the receptors. In the model system involving the visual GPCR rhodopsin, activation and phosphorylation of rhodopsin is thought to convert arrestin from a low to high affinity binding state. Phosphorylation of the M(2) muscarinic acetylcholine(More)
Multiple events are associated with the regulation of signaling by the M2 muscarinic cholinergic receptors (mAChRs). Desensitization of the attenuation of adenylyl cyclase by the M2 mAChRs appears to involve agonist-dependent phosphorylation of M2 mAChRs by G-protein coupled receptor kinases (GRKs) that phosphorylate the receptors in a serine/threonine rich(More)
Nicole looked up from her table in the teachers' lounge. She was halfway through grading her last pile of student papers, almost fi nished with the year's work. It had been an uneventful year teaching sophomore biology at Park City High School, with the usual mix of motivated students and students who would rather be doing anything other than taking a(More)
What is it? The proteasome is a multi-subunit protease complex that degrades specifically targeted proteins. Also known as¼ " the molecular chamber of doom " (see Hopkin K: J NIH Res 1997, 9:36–42). Do not call the proteasome 'the garbage disposal unit of the cell'. How are proteins directed to the chamber of doom? The proteasome recognizes and degrades(More)
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