Regulators as mediators

Regulator of G protein signaling (RGS) proteins are gatekeepers regulating the cellular responses induced by G protein-coupled receptor (GPCR)-mediated activation of heterotrimeric G proteins. Specifically, RGS proteins determine the magnitude and duration of GPCR signaling by acting as a GTPase-activating protein for Gα subunits, an activity facilitated by their semiconserved RGS domain. The R7 subfamily of RGS proteins is distinguished by two unique domains, DEP/DHEX and GGL, which mediate membrane targeting and stability of these proteins.

13p caothientrangnguyen 09-05-2020 24 1   Download

The p25rum1 is an inhibitor of Cdc2 kinase expressed in fission yeast and plays an important role in cell-cycle control. As its amino-acid sequence suggests that p25rum1 has putative phosphorylation sites for mitogen-activated protein kinase (MAPK), we investigated the ability of MAPK to phosphorylate p25rum1. Direct in vitro kinase assay using GST-fusion proteins of wild-type as well as various mutants of p25rum1 demonstrated that MAPK phosphorylates the N-terminal portion of p25rum1 and residues Thr13 and Ser19 are major phosphorylation sites for MAPK....

11p research12 01-06-2013 46 4   Download

Fructose 2,6-bisphosphate (Fru-2,6-P2 ) plays an important role in the regulation of major carbohydrate fluxes as both allosteric activator and inhibitor of target enzymes. To examine the role of Fru-2,6-P2in the regulation of hepatic carbohydrate metabolism in vivo,Fru-2,6-P2 levels were elevated in ADM mice with adenovirus-mediated overex-pression of a double mutant bifunctional enzyme, 6-phos-phofructo-2-kinase/fructose-2,6-bisphosphatase (n¼6), in comparison to normal control mice (control,n¼6). ...

9p research12 29-04-2013 50 5   Download

It has previouslybeen shown that IFN-ais apotent inhibitor of IL-2 induced proliferation in primary T-lymphocytes, by selectively abrogating the downstream e€ects of IL-2 on the core cell cycle machinery regulating the G1/S transition. Theoretically this could be mediated through cross-talk between the signalling cascades activated by these cytokines, as several signalling components are known to be shared.

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Viral infection of fibroblastic and endothelial cells leads to the transient synthesis of interferon-b(IFN-b). The down-regulation of IFN-bsynthesis after infection results both from transcriptional repression of the IFN-bgene and rapid degradation of mRNA. As with many cytokine mRNAs, IFN-bmRNA contains an AU-rich element (ARE) in its 3¢-untranslated region (UTR). AREs are known tomediate mRNAdeadenylation and destabilization. Depending on the class of ARE, deadenylation was shown to occur through synchronous or asynchronous mechanisms....

8p tumor12 20-04-2013 23 2   Download

p38 Mitogen-activated protein kinase alpha (p38 MAPKa) is a member of the MAPK family. It is activated by cellular stresses and has a number of cellular substrates whose coordinated regulation mediates inflammatory responses. In addition, it is a useful anti-inflammatory drug target that has a high specificity for Ser-Pro or Thr-Pro motifs in proteins and contains a number of transcription factors as well as protein kinases in its catalog of known substrates.

15p fptmusic 11-04-2013 42 3   Download

The double-stranded RNA-dependent protein kinase (PKR) is one of the key mediators of interferon (IFN) action against certain viruses. PKR also plays an important role in signal transduction and immunomodulation. Understanding the regulation of PKR activity is important for the use of PKR as a tool to discover and develop novel therapeutics for viral infec-tions, cancer and immune dysfunction.

0p awards 06-04-2013 25 2   Download

Research on the regulation of transcription in mammals initially focused on the mechanism of transcriptional acti-vation and
positive control of gene regulation. In contrast, transcriptional repression and
negative control of gene transcription was viewed rather as part of the
prokaryotic book of biology. However, results obtained in recent years have shown convincingly that transcriptional repression mediated by repressor proteins is a common regulatory mechanism in mammals and may play a key role in many biological processes. ...

8p dell39 03-04-2013 38 3   Download

Folding of DNA into chromatin is mediated by binding to histones such as H4; association of DNA with histones is regulated by covalent histone modifications,e.g. acetylation, methylation,andbiotinylation.We sought to identifyamino-acid residues that are biotinylated in histone H4,and to determine whether acetylation and methylation of histones affect biotinylation. Synthetic peptides spanning fragments of human histone H4 were biotinylated enzymatically using biotinidase. Peptide-bound biotin was probed with strept-avidin–peroxidase....

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The newestmember of themitogenactivatedprotein (MAP) kinase family of proteins, extracellular signal regulated kinase 5 (ERK5; also known as big-mitogen activated kinase 1 or BMK1) is widely expressed in many tissues including the brain. Although growth factor activation of ERK5 innon-neuronal cells has been shown to contribute to cell proliferation, differentiation and transformation, until recently no information was available on the role of ERK5 in neuronalsurvival.

4p dell39 03-04-2013 51 4   Download

NEDD8 is a ubiquitin-like protein that controls vital bio-logical events through its conjugation to target proteins. Previously, we identifieda negative regulator oftheNEDD8 conjugation system, NEDD8 ultimate buster-1 (NUB1), that recruits NEDD8 and its conjugates to the proteasome for degradation. Recently, we performed yeast two-hybrid screening with NUB1 as bait and isolated a ubiquitin pre-cursor UbC1 that is composed ofnine tandem repeats of a ubiquitin unit through a-peptide bonds.

11p dell39 03-04-2013 31 5   Download

During vitellogenesis, one of the most tightly regulated processes in ovipar-ous reproduction, vitellogenins are incorporated into the oocyte through vitellogenin receptor (VgR)-mediated endocytosis. In this paper, we report the cloning of the VgR cDNA from Blattella germanica, as well as the first functional analysis of VgR following an RNA interference (RNAi) approach.

11p dell39 27-03-2013 40 1   Download

SOCS3 is a negative regulator of cytokine signalling that inhibits Janus kinase-signal transduction and activator of transcription (JAK-STAT) mediated signal tranduction by binding to phosphorylated tyrosine residues on intracellular subunits of various cytokine receptors, as well as possibly the JAK proteins.

11p dell39 27-03-2013 41 5   Download

The notion that it takes two to tango is certainly true for leukocyte trans-endothelial migration. A growing pallet of leukocyte adhesion-induced signaling events in endothelial cells have been identified, mediating both short-term (i.e. permeability) as well as long-term (i.e. regulation of tran-scription) effects.

8p inspiron33 25-03-2013 34 6   Download

Thrombopoietin is the primary regulator of platelet production. We exploi-ted two naturally occurring miniproteins of the inhibitor cystine knot fam-ily as stable and rigid scaffolds for the incorporation of peptide sequences that have been shown to act as high-affinity thrombopoietin antagonists. Several miniproteins that antagonistically block thrombopoietin-mediated receptor activation were identified using a microscale reporter assay.

10p inspiron33 23-03-2013 32 4   Download

Tissue-type plasminogen activator (t-PA) has recently been identified as a modulator of neuronal plasticity and can initiate conversion of the pro-form of brain-derived neurotrophic factor (BDNF) into its mature form. BDNF also increases t-PA gene expression implicating t-PA as a downstream effector of BDNF function.

13p galaxyss3 19-03-2013 65 3   Download

The collapsin response mediator protein 2 (CRMP-2) is a central molecule regulating axonal growth cone guidance. It interacts with the cytoskeleton and mediates signals related to myelin-induced axonal growth inhibition. CRMP-2 has also been characterized as a constituent of neurofibrillary tangles in Alzheimer’s disease.

14p galaxyss3 07-03-2013 40 5   Download

Mitochondria, which are the cellular energy plants, also act as the integra-tion center of cellular signaling pathways. Apoptosis is a well-known pathway in which mitochondria are involved. Protein kinase Cehas been classified as a novel type of protein kinase C and is involved in many cellular events regulating mitochondrial function.

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Ceramide (Cer) is known to be a lipid mediator in apoptosis and to have an important role in cell fate, via control of intracellular Cer levels. Recently, ceramide kinase (CerK) was identified as an enzyme that converts Cer to ceramide 1-phosphate (C1P). We examined potential functions of CerK in the regulation of keratinocyte survival, and the possible involve-ment of peroxisome proliferator-activated receptor beta (PPARb).

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Dinucleoside polyphosphates (NpnN¢s; where N and N¢ are nucleosides andn= 3–6 phosphate residues) are naturally occurring compounds that may act as signaling molecules. One of the most successful approaches to understand their biological functions has been through the use of NpnN¢ analogs.

11p vinaphone15 27-02-2013 42 3   Download