RGS proteins are negative regulators of signaling through heterotrimeric G protein-coupled receptors and, as such, are in a position to regulate a plethora of biological phenomena. However, those have just begun to be explored in vivo. Here, we describe a mouse line deficient for Rgs4, a gene normally expressed early on in discrete populations of differentiating neurons and later on at multiple...

Protease-activated receptor 1 (PAR1) is a G-protein coupled receptor (GPCR) that is activated by natural proteases to regulate many physiological actions. We previously reported that PAR1 couples to Gi, Gq and G12 to activate linked signaling pathways. Regulators of G protein signaling (RGS) proteins serve as GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins inte...

The pro-inflammatory cytokine IL-1beta contributes to the reduced contractile responses of gut smooth muscle observed in both animal colitis models and human inflammatory bowel diseases. However, the mechanisms are not well understood. The effects of IL-1beta on the signaling targets mediating acetylcholine (ACh)-induced initial and sustained contraction were examined using rabbit colonic circu...

Initial Ca(2+)-dependent contraction of intestinal smooth muscle is inhibited upon IL-1beta treatment. The decrease in contraction reflects the upregulation of regulator of G protein signaling-4 (RGS4) via the canonical inhibitor of NF-kappaB kinase-2 (IKK2)/IkappaB-alpha/NF-kappaB pathway. Here, we show that the activation of various protein kinases, including ERK1/2, p38 MAPK, and phosphoinos...

Circulating free fatty acids are a reflection of the balance between lipogenesis and lipolysis that takes place mainly in adipose tissue. We found that mice deficient for regulator of G protein signaling (RGS)-4 have increased circulating catecholamines, and increased free fatty acids. Consequently, RGS4-/- mice have increased concentration of circulating free fatty acids; abnormally accumulate...

Introduction: Regulators of G-protein signaling protein negatively control G protein -coupled receptor signaling duration by accelerating Gα subunit guanosine triphosphate hydrolysis . Since regulator of G-protein signaling4 has an important role in modulating morphine effects at the cellular level and the exact mechanism(s) of adrenalectomy-induced morphine sensitization have not been fully cl...

Regulators of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Gi but not by Gs class alpha-subunits. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. We have demonstrated that the RGS domains of RGS4, RGS10, and GAIP retain GTPase accelerating activity with the Gi class substrates Gialpha1, Goalpha, and Gzalpha in vitro. No regulatory activity of...

Regulators of G protein signaling (RGS) proteins limit the lifetime of activated (GTP-bound) heterotrimeric G protein a subunits by acting as GTPase-activating proteins (GAPs). Mutation of two residues in RGS4, which, based on the crystal structure of RGS4 complexed with G(i alpha1)-GDP-AIF4-, directly contact G(i alpha1) (N88 and L159), essentially abolished RGS4 binding and GAP activity. Muta...

Metabotropic glutamate receptors (mGluRs) couple to heterotrimeric G-proteins and regulate cell excitability and synaptic transmission in the CNS. Considerable effort has been focused on understanding the cellular and biochemical mechanisms that underlie regulation of signaling by G-proteins and their linked receptors, including the mGluRs. Recent findings demonstrate that regulators of G-prote...

Hu W, Li F, Mahavadi S, Murthy KS. Upregulation of RGS4 expression by IL-1 in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3 pathway. Am J Physiol Cell Physiol 296: C1310–C1320, 2009; doi:10.1152/ajpcell.00573.2008.—Initial Ca -dependent contraction of intestinal smooth muscle is inhibited upon IL-1 treatment. The decrease in contraction reflects the...