ArhGAP9, a novel MAP kinase docking protein, inhibits Erk and p38 activation through WW domain binding

Ang, Boon Keong; Lim, Cheng‐Chew; Koh, Sharon S; Sivakumar, Neelamegam; Taib, Shahrizan; Lim, Kim B; Ahmed, Sohail; Rajagopal, G.; Ong, Siew Hwa

doi:10.1186/1750-2187-2-1

Cited by 34 publications

(33 citation statements)

References 58 publications

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“…Q-PCR validation of the most promising target genes revealed that (in agreement with our cell physiology data) expression of lipid synthesis-related (NRIP1 and ARHGAP9) and proliferation-related (MKI67) genes was altered in a TRPV4-dependent manner, whereas changes in the expression of "inflammation" genes were found to be TRPV4 independent ( Figure 6C). Moreover, alterations of ARHGAP9 expression (a known endogenous inhibitor of ERK signaling) (46) suggested that inhibition of the prolipogenic MAPK pathway (12) might play a role in mediating the lipostatic effects of CBD. Indeed, we found that CBD inhibited AEA-induced (prolipogenic) (12) ERK1/2 phosphorylation in a TRPV4-dependent manner ( Figure 7A), confirming again the crucial role of TRPV4 in mediating the action of CBD.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Oláh¹,

Tóth²,

Borbíró³

et al. 2014

J. Clin. Invest.

230

236

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Section: Discussionmentioning

confidence: 99%

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Oláh¹,

Tóth²,

Borbíró³

et al. 2014

J. Clin. Invest.

230

236

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“…Within cells, σ 1 -receptors can be found on the endoplasmic reticulum, mitochondria, nuclear membrane envelope and plasma membrane [2]; their localization at the interface of the endoplasmic reticulum and mitochondria has become the focus of recent research [30]. Following the binding of ligands to it, the σ 1 -receptor can translocate between different cellular compartments and form protein–protein interactions to modulate the activities of G-protein-coupled receptors (GPCR), ion channels and signaling molecules [2,12,30–32]. …”

Section: Sigma Receptor Subtypesmentioning

confidence: 99%

Targeting sigma receptors: novel medication development for drug abuse and addiction

Matsumoto¹

2009

Expert Review of Clinical Pharmacology

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Psychostimulant abuse is a serious health and societal problem in industrialized and developing countries. However, the identification of an effective pharmacotherapy to treat it has remained elusive. It has long been known that many psychostimulant drugs, including cocaine and methamphetamine, interact with sigma receptors in the brain and heart, offering a logical target for medication development efforts. However, selective pharmacological agents and molecular biological tools have only recently become available to rigorously evaluate these receptors as viable medication development targets. The current review will summarize provocative preclinical data, demonstrating the ability of sigma receptor antagonists and antisense oligonucleotides to ameliorate cocaine-induced convulsions, lethality, locomotor activity and sensitization, and conditioned place-preference in rodents. Recent studies suggest that the protective effects of sigma receptor antagonists also extend to actions produced by methamphetamine, 3,4-methylenedioxymethamphetamine, ethanol and other abused substances. Together, the data indicate that targeting sigma receptors, particularly the σ1-subtype, may offer an innovative approach for combating the effects of cocaine, and perhaps other abused substances.

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“…Due to the constitutive PIP 2 availability in resting cells, these PIP 2 -associated proteins likely maintain signaling pathways in a pre-activation state. Evidence supporting this notion in T cells comes from the inhibitory effects of PIP 2 binding to the guanine nucleotide exchange factor, Vav (Han et al 1998) and the guanine nucleotide activating factor, ArhGAP9, which maintains Rho-family GTPases in an inactive state (Ang et al 2007; Ceccarelli et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Lipid Signaling in T-Cell Development and Function

Huang

Sauer

2010

Cold Spring Harbor Perspectives in Biology

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Second messenger molecules relay, amplify, and diversify cell surface receptor signals. Two important examples are phosphorylated D-myo-inositol derivatives, such as phosphoinositide lipids within cellular membranes, and soluble inositol phosphates. Here, we review how phosphoinositide metabolism generates multiple second messengers with important roles in T-cell development and function. They include soluble inositol(1,4,5)trisphosphate, long known for its Ca 2þ -mobilizing function, and phosphatidylinositol(3,4,5)trisphosphate, whose generation by phosphoinositide 3-kinase and turnover by the phosphatases PTEN and SHIP control a key "hub" of TCR signaling. More recent studies unveiled important second messenger functions for diacylglycerol, phosphatidic acid, and soluble inositol(1,3,4,5)tetrakisphosphate (IP 4 ) in immune cells. Inositol(1,3,4,5)tetrakisphosphate acts as a soluble phosphatidylinositol(3,4,5)trisphosphate analog to control protein membrane recruitment. We propose that phosphoinositide lipids and soluble inositol phosphates (IPs) can act as complementary partners whose interplay could have broadly important roles in cellular signaling.S econd messenger molecules relay, amplify, and diversify signals perceived by cell surface receptors. One important second messenger family is comprised of the phosphorylated derivatives of the small cyclic poly-alcohol Dmyo-inositol. They include phosphoinositide lipids within cellular membranes, and soluble inositol phosphates, here termed IPs. In most stimulatory cells, the plasma membrane phosphoinositide, phosphatidylinositol(4,5)bisphosphate (here termed PIP 2 for improved readability, although several different PIP 2 isomers exist) is a key precursor for both other phosphoinositides and soluble IPs. Many of these regulate distinct and overlapping down-

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ArhGAP9, a novel MAP kinase docking protein, inhibits Erk and p38 activation through WW domain binding

Cited by 34 publications

References 58 publications

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

Targeting sigma receptors: novel medication development for drug abuse and addiction

Lipid Signaling in T-Cell Development and Function

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