RGS Protein Specificity Towards Gq- and Gi/o-Mediated ERK 1/2 and Akt Activation, in vitro

T Anger, N Klintworth, C Stumpf, WG Daniel… - BMB …, 2007 - koreascience.kr
T Anger, N Klintworth, C Stumpf, WG Daniel, U Mende, CD Garlichs
BMB Reports, 2007koreascience.kr
Abstract Extracellular Regulated Kinases (ERK) and Protein Kinase B (Akt) are
intermediaries in relaying extracellular growth signals to intracellular targets. Each pathway
can become activated upon stimulation of G protein-coupled receptors mediated by $ G_q $
and $ G_ {i/o} $ proteins subjected to regulation by RGS proteins. The goal of the study was
to delineate the specificity in which cardiac RGS proteins modulate $ G_ {q^-} $ and $ G_
{i/o} $-induced ERK and Akt phosphorylation. To isolate $ G_ {q^-} $ and $ G_ {i/o} …
Abstract
Extracellular Regulated Kinases (ERK) and Protein Kinase B (Akt) are intermediaries in relaying extracellular growth signals to intracellular targets. Each pathway can become activated upon stimulation of G protein-coupled receptors mediated by and proteins subjected to regulation by RGS proteins. The goal of the study was to delineate the specificity in which cardiac RGS proteins modulate and -induced ERK and Akt phosphorylation. To isolate and -mediated effects, we exclusively expressed muscarinic or receptors in COS-7 cells. Western blot analyses demonstrated increase of phosphorylation of ERK 1.7-/3.3-fold and Akt 2.4-/6-fold in expressing cells through carbachol stimulation. In co-expressions, -induced activation of Akt was exclusively blunted through RGS3s/RGS3, whereas activation of ERK was inhibited additionally through RGS2/RGS5. induced Akt activation was inhibited by all RGS proteins tested. RGS2 had no effect on -induced ERK activation. The high degree of specificity in RGS proteins-depending modulation of and -mediated ERK and Akt activation in the muscarinic network cannot merely be attributed exclusively to RGS protein selectivity towards or proteins. Counter-regulatory mechanisms and inter-signaling cross-talk may alter the sensitivity of GPCR-induced ERK and Akt activation to RGS protein regulation.
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