P90 Ribosomal S6 kinase 2, a novel GPCR kinase, is required for growth factor-mediated attenuation of GPCR signaling.

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-deriv

SUBMITTER: Strachan RT 

PROVIDER: S-EPMC3107544 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature