Differential Requirement of Gα12, Gα13, Gαq, and Gβγ for Endothelin-1-Induced c-Jun NH2-Terminal Kinase and Extracellular Signal-Regulated Kinase Activation

Arai, Ken; Maruyama, Yoshiko; Nishida, Motohiro; Tanabe, Shihori; Takagahara, Shuichi; Kozasa, Tohru; Mori, Yasuo; Nagao, Taku; Kurose, Hitoshi

doi:10.1124/mol.63.3.478

Cited by 71 publications

(49 citation statements)

References 33 publications

(34 reference statements)

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“…UDP stimulated the accumulation of phosphorylated VASP to the plasma membrane in a time-dependent manner, which peaked at 3 to 10 min after stimulation and correlated with the time course of actin aggregation RGS, which binds G 12/13 and inhibits downstream signaling pathway, but not by the negative mutant form of p115-RGS (mut-RGS) (Fig. 4c) [20][21][22][23]. These data indicate that Rho GTPase is involved in UDP-induced VASP phosphorylation and actin aggregating effects.…”

Section: Udp-induced Actin Aggregation and Vasp Phosphorylation Were mentioning

confidence: 90%

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

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Microglia are major immunocompetent cells in the central nervous system and retain highly dynamic motility. The processes which allow these cells to move, such as chemotaxis and phagocytosis, are considered part of their functions and are closely related to purinergic signaling. Previously, we reported that the activation of the P2Y 6 receptor by UDP stimulation in microglia evoked dynamic cell motility which enhanced their phagocytic capacity, as reported by Koizumi et al. (Nature 446 (7139):1091-1095. These responses require actin cytoskeletal rearrangement, which is seen after UDP stimulation. However, the intracellular signaling pathway has not been defined. In this study, we found that UDP in rat primary microglia rapidly induced the transient phosphorylation at Ser157 of vasodilator-stimulated phosphoprotein (VASP). VASP, one of actin binding protein, accumulated at the plasma membrane where filamentous (F)-actin aggregated in a time-dependent manner. The phosphorylation of VASP was suppressed by inhibition of PKC. UDP-induced local actin aggregations were also abrogated by PKC inhibitors. The Rho inhibitor CT04 and the expression of p115-RGS, which suppresses G 12/13 signaling, attenuated UDP-induced phosphorylation of VASP and actin aggregation. These results indicate that PKC-and Rho-dependent phosphorylation of VASP is involved in UDP-induced actin aggregation of microglia.

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Section: Udp-induced Actin Aggregation and Vasp Phosphorylation Were mentioning

confidence: 90%

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

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“…The cDNA coding G12VRap1, a constitutively active form of Rap1, containing FLAG in Adeno-X Expression System (Fukuhara et al, 2005) was used for recombinant adenovirus construction. The recombinant adenovirus for T19NRhoA, a dominant-negative form of RhoA, and p115RGS, an RGS domain of p115RhoGEF, were constructed as described previously (Arai et al, 2003). The adenovirus expressing green fluorescent protein (GFP) was used for evaluation of the expression by visualization.…”

Section: Construction Of Adenoviral Vector and Infection Of Recombinamentioning

confidence: 99%

Role of Rap1B and Tumor Suppressor PTEN in the Negative Regulation of Lysophosphatidic Acid—induced Migration by Isoproterenol in Glioma Cells

Malchinkhuu

Sato

Maehama

et al. 2009

MBoC

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The clarification of mechanisms that negatively regulate the invasive behavior of human glioma cells is of great importance in order to find new methods of treatment. In this study, we have focused on the negative regulation of lysophosphatidic acid (LPA)-induced migration in glioma cells. Using small interference RNA and dominant-negative gene strategies in addition to pharmacological tools, we found that isoproterenol (ISO) and sphingosine-1-phosphate (S1P) negatively but differently regulate the LPA-induced migration. ISO-induced suppression of the migration of glioma cells occurs via ␤ 2 -adrenergic receptor/cAMP/Epac/Rap1B/inhibition of Rac, whereas S1P has been shown to suppress the migration of the cells through S1P 2 receptor/Rho-mediated down-regulation of Rac1. The expression of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is required for the inhibitory ISO-induced and Rap1B-mediated actions on the migration, Rac1 activation, and Akt activation in response to LPA. Thus, the PTENmediated down-regulation of phosphatidylinositol 3-kinase activity may be involved in the regulation of Rap1B-dependent inhibition of Rac1 activity. These findings suggest that there are at least two distinct inhibitory pathways, which are mediated by the S1P 2 receptor and ␤ 2 -adrenergic receptor, to control the migratory, hence invasive, behavior of glioma cells. INTRODUCTIONThe malignant astrocytomas, the anaplastic astrocytoma and glioblastoma multiforme, are the most common glial tumors, with an annual incidence of three to four per 100,000 of population (DeAngelis, 2001). Because radical surgical treatment of malignant glial tumors is impossible because of the highly expressed migratory and invasive features of glioma cells, further understanding of the complex regulation and signaling molecules involved in glioma invasion is still needed. Lysophosphatidic acid (LPA) has been shown to play a significant role in human tumorigenesis as a factor to increase the motility and invasiveness of different cell types (Imamura et al., 1993;Stam et al., 1998). In glioma cells as well, extracellularly added LPA induced the proliferation and migration of stimulated cells (Malchinkhuu et al., 2005). A major part of extracellular LPA is thought to be produced from lysophosphatidylcholine by autotaxin/lysophospholipase D (Tokumura et al., 2002;Umezu-Goto et al., 2002). In the CNS as well, LPA production seems to occur in a similar way . Recent evidence suggested that autotaxin is overexpressed in glioblastoma multiforme and contributes to the cell motility of glioblastomas (Kishi et al., 2006). For this reason, revealing new substances or mechanisms that could negatively regulate the LPA-induced invasive behavior is of great importance for devising new and effective treatment modalities to counteract tumor cells.Our previous studies (Malchinkhuu et al., 2005(Malchinkhuu et al., , 2008 and those from other laboratories (Lepley et al., 2005) suggest that sphingosine 1-phosphate (S1P) and its receptors are ...

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“…The recombinant adenovirus for a dominant-negative form of RhoA, T19NRhoA, and a constitutively active form of RhoA, G14VRhoA, was constructed (27) and infected (21) as described previously. In brief, 80% confluent HUVECs were infected with recombinant at a multiplicity of infection of 30 for 2 h at 37°C in RPMI 1640 containing 5% FBS.…”

Section: Construction Of Adenoviral Vector and Infection Of Recombinamentioning

confidence: 99%

Induction of Scavenger Receptor Class B Type I Is Critical for Simvastatin Enhancement of High-Density Lipoprotein-Induced Anti-Inflammatory Actions in Endothelial Cells

Kimura

Mogi

Tomura

et al. 2008

The Journal of Immunology

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Changes in plasma lipoprotein profiles, especially low levels of high-density lipoprotein (HDL), are a common biomarker for several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis. We examined the effect of simvastatin on HDL-induced anti-inflammatory actions. HDL and sphingosine 1-phosphate (S1P), a bioactive lipid component of the lipoprotein, inhibited TNF α-induced expression of VCAM-1, which was associated with NO synthase (NOS) activation, in human umbilical venous endothelial cells. The HDL- but not S1P-induced anti-inflammatory actions were enhanced by a prior treatment of the cells with simvastatin in a manner sensitive to mevalonic acid. Simvastatin stimulated the expression of scavenger receptor class B type I (SR-BI) and endothelial NOS. As for S1P receptors, however, the statin inhibited the expression of S1P3 receptor mRNA but caused no detectable change in S1P1 receptor expression. The reconstituted HDL, a stimulator of SR-BI, mimicked HDL actions in a simvastatin-sensitive manner. The HDL- and reconstituted HDL-induced actions were blocked by small interfering RNA specific to SR-BI regardless of simvastatin treatment. The statin-induced expression of SR-BI was attenuated by constitutively active RhoA and small interfering RNA specific to peroxisome proliferator-activated receptor-α. Administration of simvastatin in vivo stimulated endothelial SR-BI expression, which was accompanied by the inhibition of the ex vivo monocyte adhesion in aortas from TNF α-injected mice. In conclusion, simvastatin induces endothelial SR-BI expression through a RhoA- and peroxisome proliferator-activated receptor-α-dependent mechanism, thereby enhancing the HDL-induced activation of NOS and the inhibition of adhesion molecule expression.

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Differential Requirement of Gα₁₂, Gα₁₃, Gα_q, and Gβγ for Endothelin-1-Induced c-Jun NH₂-Terminal Kinase and Extracellular Signal-Regulated Kinase Activation

Cited by 71 publications

References 33 publications

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Role of Rap1B and Tumor Suppressor PTEN in the Negative Regulation of Lysophosphatidic Acid—induced Migration by Isoproterenol in Glioma Cells

Induction of Scavenger Receptor Class B Type I Is Critical for Simvastatin Enhancement of High-Density Lipoprotein-Induced Anti-Inflammatory Actions in Endothelial Cells

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