Gene expression analyses of postmortem cerebral cortex suggest that transcription of the regulator of G-protein signaling 4 (RGS4) is decreased in a diagnosis-specific manner in subjects with schizophrenia. To evaluate the possible role of RGS4 in the pathogenesis of schizophrenia, we conducted genetic association and linkage studies using samples ascertained independently in Pittsburgh and New...

N-terminally green fluorescent protein (GFP)-tagged regulator of G protein signaling (RGS) 2 and RGS4 fusion proteins expressed in human embryonic kidney 293 cells localized to the nucleus and cytosol, respectively. They were selectively recruited to the plasma membrane by G proteins and correspondingly by receptors that activate those G proteins: GFP-RGS2 when coexpressed with Galphas, beta2-a...

Regulators of G-protein signaling (RGS) accelerate guanine triphosphate hydrolysis by Galpha-subunits and profoundly inhibit signaling by G protein-coupled receptors. The distinct expression patterns and pathophysiologic regulation of RGS proteins suggest that inhibitors may have therapeutic potential. We previously reported the design of a constrained peptide inhibitor of RGS4 (1: Ac-Val-Lys-[...

In the arginylation branch of the N-end rule pathway, unacetylated N-terminal destabilizing residues function as essential determinants of protein degradation signals (N-degron). Here, we show that a neurostimulant, para-chloroamphetamine (PCA), specifically inhibits the Arg/N-end rule pathway, delaying the degradation of its artificial and physiological substrates, including regulators of G pr...

BACKGROUND RGS family members are GTPase-activating proteins for heterotrimeric Gq and Gi proteins. RGS genes are expressed in heart tissue and in cultured cardiomyocytes. There is evidence that altered RGS gene expression may contribute to the pathogenesis of cardiac hypertrophy and failure. METHODS AND RESULTS We investigated the ability of RGS proteins to block G-protein signaling in vivo ...

The expression of predominant housekeeping genes used in RT-qPCR can vary during development and differentiation. The frequently used housekeeping genes (ACTB, GAPDH, 18S rRNA, EF1α and RPL 13a) were evaluated during an early stage of the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (mMSCs) (under normal conditions or treated with CCG-4986) to identify housekee...

Diffuse brain invasion is a major reason for poor prognosis of glioma patients. The molecular mechanisms underlying infiltration are different from those of other cancer types. To detect genes associated with glioma invasion, highly migratory clones were selected from U373MG glioma cells and from primary glioblastoma cells, and the gene expression pattern of these "fast" cells was compared with...

Chronic alcoholism leads to neurotoxic effects in the central nervous system. Neuroadaptive changes in the brain may lead to tolerance to, and dependence on, alcohol as a result of alterations in synaptic complexity. G-proteins are negatively regulated by RGS proteins, which are integral to many neural pathways that include neurotransmission, hormonal responses, and chemotactic signals. These c...

Diabetic patients develop a cardiomyopathy that consists of ventricular hypertrophy and diastolic dysfunction. Although the pathogenesis of this condition is poorly understood, previous studies implicated abnormal G-protein activation. In this work, mice with cardiac overexpression of the transcription factor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) were examined as a model...

Mice lacking the gene encoding fragile X mental retardation protein (FMR1) are susceptible to audiogenic seizures, and antagonists of the group I metabotropic glutamate receptors (mGluRs) have been shown to block seizures in FMR1 knockout mice. We investigated whether the G-protein-inhibitory activity of the regulator of G-protein signaling protein, RGS4, could also alter the susceptibility to ...