p90 Ribosomal S6 kinase 2, a novel GPCR kinase, is required for growth factor-mediated attenuation of GPCR signaling.

Biochemistry
Ryan T StrachanB L Roth

Abstract

The 5-hydroxytryptamine 2A (5-HT(2A)) receptor is a member of the G protein-coupled receptor superfamily (GPCR) and plays a key role in transducing a variety of cellular signals elicited by serotonin (5-HT; 5-hydroxytryptamine) in both peripheral and central tissues. Recently, we discovered that the ERK/MAPK effector p90 ribosomal S6 kinase 2 (RSK2) phosphorylates the 5-HT(2A) receptor and attenuates 5-HT(2A) receptor signaling. This raised the intriguing possibility of a regulatory paradigm whereby receptor tyrosine kinases (RTKs) attenuate GPCR signaling (i.e., "inhibitory cross-talk") by activating RSK2 [Strachan et al. (2009) J. Biol. Chem. 284, 5557-5573]. We report here that activation of multiple endogenous RTKs such as the epidermal growth factor receptor (EGFR), the platelet-derived growth factor receptor (PDGFR), and ErbB4 significantly attenuates 5-HT(2A) receptor signaling in a variety of cell types including mouse embryonic fibroblasts (MEFs), mouse vascular smooth muscle cells (mVSMCs), and primary cortical neurons. Importantly, genetic deletion of RSK2 completely prevented signal attenuation, thereby suggesting that RSK2 is a critical mediator of inhibitory cross-talk between RTKs and 5-HT(2A) receptors. We also ...Continue Reading

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Citations

Sep 28, 2010·Annual Review of Pharmacology and Toxicology·John A Allen, Bryan L Roth
Sep 11, 2010·European Journal of Pharmacology·J Adolfo García-SáinzLuz del Carmen Medina
Oct 27, 2015·Frontiers in Pharmacology·Gongliang Zhang, Robert W Stackman
Jun 11, 2011·Biochimie·Valéria Ernestânia ChavesNair Honda Kawashita
Oct 5, 2012·Molecular Pharmacology·Ishier RaoteMitradas M Panicker
Jun 8, 2018·Frontiers in Behavioral Neuroscience·Matthias Fischer, Thomas Raabe
Jul 26, 2021·Cellular Signalling·Srikanth PalanisamyKathleen Gabrielson

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