Evidence That Gα<sub>q</sub>-Coupled Receptor-Induced Interleukin-6 mRNA in Vascular Smooth Muscle Cells Involves the Nuclear Factor of Activated T Cells

Abbott, Karen L.; Loss, James R.; Robida, Aaron M.; Murphy, Thomas J.

doi:10.1124/mol.58.5.946

Cited by 45 publications

(38 citation statements)

References 39 publications

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“…A number of groups have shown that ATP and other nucleotides can elicit transient or sustained Ca 2+ signals in a variety of other cell types (Oshimi et al, 1999;Möller et al, 2000;Nobile et al, 2003;Korcok et al, 2004). The role of the Ca 2+ -regulated NFAT transcription factors in P2 receptor signaling has also been examined previously (Ferrari et al, 1999;Abbott et al, 2000;Kataoka et al, 2009;Shiratori et al, 2010). However, no previous studies have employed a concentration range capable of revealing the relationship between ATP dose and Ca 2+ -NFAT signal duration described in the present study.…”

Section: P2 Receptor Network Enable Dose-to-duration Encoding Of Ca mentioning

confidence: 55%

P2 receptor networks regulate signaling duration over a wide dynamic range of ATP concentrations

Grol

Pereverzev²,

Sims³

et al. 2013

Journal of Cell Science

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SummaryThe primordial intercellular signaling molecule ATP acts through two families of cell-surface P2 receptors -the P2Y family of Gprotein-coupled receptors and the P2X family of ligand-gated cation channels. Multiple P2 receptors are expressed in a variety of cell types. However, the significance of these networks of receptors in any biological system remains unknown. Using osteoblasts as a model system, we found that a low concentration of ATP (10 mM, ATP low ) induced transient elevation of cytosolic Ca 2+ , whereas a high concentration of ATP (1 mM, ATP high ) elicited more sustained elevation. Moreover, graded increases in the Ca 2+ signal were achieved over a remarkable million-fold range of ATP concentrations (1 nM to 1 mM). Next, we demonstrated that ATP low caused transient nuclear localization of the Ca 2+ -regulated transcription factor NFATc1; whereas, ATP high elicited more sustained localization. When stimulated with ATP high , osteoblasts from P2X7 loss-of-function mice showed only transient Ca 2+ -NFATc1 signaling; in contrast, sustained signaling was observed in wild-type cells. Additional experiments revealed a role for P2Y receptors in mediating transient signaling induced by low ATP concentrations. Thus, distinct P2 receptors with varying affinities for ATP account for this wide range of sensitivity to extracellular nucleotides. Finally, ATP high , but not ATP low , was shown to elicit robust expression of the NFAT target gene Ptgs2 (encoding COX-2), consistent with a crucial role for the duration of Ca 2+ -NFAT signaling in regulating target gene expression. Taken together, ensembles of P2 receptors provide a mechanism by which cells sense ATP over a wide concentration range and transduce this input into distinct cellular signals.

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Section: P2 Receptor Network Enable Dose-to-duration Encoding Of Ca mentioning

confidence: 55%

P2 receptor networks regulate signaling duration over a wide dynamic range of ATP concentrations

Grol

Pereverzev²,

Sims³

et al. 2013

Journal of Cell Science

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“…With EGF treatment, B80% confluent cells were cultured in serum-free medium overnight in 24-well plates prior to addition of EGF Â 5 h. With transient introduction of the PKC-d constructs, cells were serum starved for 24 h following transfection. Luciferase activity was measured as described earlier (Abbott et al, 2000;Xu and Shu, 2007).…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-δ

Chang

Gao

et al. 2009

Oncogene

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Earlier, we showed that epidermal growth factor receptor (EGFR) signaling in human glioma cells increased cyclooxygenase-2 (COX-2) expression through p38-mitogen-activated protein kinase (MAPK)-dependent activation of the Sp family of transcription factors. Further mechanistic details of EGFR-dependent induction of COX-2 expression in glioma cells remained elusive. Protein kinase Cs (PKCs) comprise a family of serine-threonine kinases that are major mediators of signaling from receptor tyrosine kinases. Here, we report that PKC-d, a novel PKC isoform, plays a role in EGF-dependent COX-2 induction in human glioma cells. Pharmacological inhibition and genetic silencing (through siRNA or dominantnegative expression) of PKC-d confirm a role for this PKC isoform in EGF-dependent COX-2 induction. Overexpression of a functional PKC-d enhanced COX-2 expression indicating that PKC-d is not only necessary but also sufficient to regulate COX-2 levels. Inhibition of p38-MAPK pharmacologically or with siRNA further shows that p38-MAPK is required for activation of PKC-d by EGF while inhibition of PKC-d had no discernible effects on p38-MAPK activation. Finally, EGF stimulation promotes physical interactions between PKC-d and Sp1 resulting in phosphorylation and nuclear localization of this transcription factor. These data provide the first evidence that PKC-d is a critical link between p38-MAPK and Sp1-dependent COX-2 expression in human glioma cells.

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“…In addition, they induce ROS production through NAD(P)H oxidase (13). Several transcription factors, such as NFAT, AP-1, cAMP-responsive element-binding protein, serum-responsive factor, STAT, and NFB are induced in UTP-stimulated SMCs (14), controlling the expression of a set of genes including OPN (10). Moreover, we have demonstrated previously that nucleotide-induced SMC migration is dependent on OPN expression and on its binding to the ␣ v ␤ 3 integrin (6).…”

mentioning

confidence: 99%

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

Renault

Jalvy

Potier

et al. 2005

Journal of Biological Chemistry

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Osteopontin (OPN) is an important chemokinetic agent for several cell types. Our earlier studies have shown that its expression is essential for uridine triphosphate (UTP)-mediated migration of vascular smooth muscle cells. We demonstrated previously that the activation of an AP-1 binding site located 76 bp upstream of the transcription start in the rat OPN promoter is involved in the induction of OPN expression. In this work, using a luciferase promoter deletion assay, we identified a new region of the rat OPN promoter (؊1837 to ؊1757) that is responsive to UTP. This region contains an NFB site located at ؊1800 and an Ebox located at ؊1768. Supershift electrophoretic mobility shift assay and chromatin immunoprecipitation assays identified NFB and USF-1/USF-2 as the DNA binding proteins induced by UTP, respectively, for these two sites. Using dominant negative mutants of IB kinase and USF transcription factors, we confirmed that NFB and USF-1/USF-2 are involved in the UTP-mediated expression of OPN. Using a pharmacological approach, we demonstrated that USF proteins are regulated by the extracellular signal-regulated kinase (ERK)1/2 pathway, just as the earlier discovered AP-1 complex, whereas NFB is up-regulated through PKC␦ signals. Finally, our work suggests that the UTPstimulated OPN expression involves a coordinate regulation of PKC␦-NFB, ERK1/2-USF, and ERK1/2/ NAD(P)H oxidase AP-1 signaling pathways. Osteopontin (OPN)1 is a multifunctional phosphoprotein secreted by many cell types such as osteoclasts, lymphocytes, macrophages, epithelial cells, and smooth muscle cells (SMCs).Its expression is induced during vessel remodeling, as well as wound healing and bone synthesis (1). Overexpression of OPN can be found in pathological settings, such as immunological disorders, neoplastic transformation, metastasis, and formation of urinary stones. Its role in cell migration has been established in vitro in various cell types, including osteoclasts (2), macrophages (3), endothelial cells (4), and SMCs (5, 6). In vivo studies have established that OPN contributes to SMC recruitment into atherosclerotic plaques (7) and neointimal thickening (8), to osteoclast recruitment during bone resorption, (2) and to macrophage recruitment at inflammatory sites (atherosclerotic plaque, granulomas) (3).In the context of vascular remodeling, soluble factors, such as angiotensin II, basic fibroblast growth factor, plateletderived growth factor, interleukin-1 (9), and the nucleotides ATP and UTP (10), all induce expression of OPN. Moreover, nucleotides also modulate contraction, proliferation, and migration of vascular SMCs (11). They act through G proteincoupled P2Y receptors (12) and activate phospholipase C, resulting in elevated levels of intracellular free Ca 2ϩ and activation of PKC. In addition, they induce ROS production through NAD(P)H oxidase (13). Several transcription factors, such as NFAT, AP-1, cAMP-responsive element-binding protein, serum-responsive factor, STAT, and NFB are induced in UTP-stimulated SMCs (14), contro...

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Evidence That Gα_q-Coupled Receptor-Induced Interleukin-6 mRNA in Vascular Smooth Muscle Cells Involves the Nuclear Factor of Activated T Cells

Cited by 45 publications

References 39 publications

P2 receptor networks regulate signaling duration over a wide dynamic range of ATP concentrations

P2 receptor networks regulate signaling duration over a wide dynamic range of ATP concentrations

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-δ

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

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Evidence That Gαq-Coupled Receptor-Induced Interleukin-6 mRNA in Vascular Smooth Muscle Cells Involves the Nuclear Factor of Activated T Cells

Cited by 45 publications

References 39 publications

P2 receptor networks regulate signaling duration over a wide dynamic range of ATP concentrations

P2 receptor networks regulate signaling duration over a wide dynamic range of ATP concentrations

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-δ

UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells

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Evidence That Gα_q-Coupled Receptor-Induced Interleukin-6 mRNA in Vascular Smooth Muscle Cells Involves the Nuclear Factor of Activated T Cells