Activation of G12/G13 Results in Shape Change and Rho/Rho-Kinase–mediated Myosin Light Chain Phosphorylation in Mouse Platelets

Klages, Birgit; Brandt, Ursula; Simon, Melvin I.; Schultz, Günter; Offermanns, Stefan

doi:10.1083/jcb.144.4.745

Cited by 329 publications

(328 citation statements)

References 72 publications

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“…Interaction of SW480 and CT26 with ADAM10 stimulates RhoA activity As the interaction of Ga13 with RhoA leads to an increase in cell cortical tension as well as in disruption of plasma membrane-cortical actin, 22,23 we investigated whether the interaction of SW480 and CT26 cells with ADAM10Cys-EGFP or ADAM10-EGFP activates Rho small GTPase. To this end, we performed a GTP-RhoA pull-down assay.…”

Section: Adam10 and Cd81 Regulate Localization Of Gtp-binding A13mentioning

confidence: 99%

Cell fusion promotes chemoresistance in metastatic colon carcinoma

et al. 2012

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Chemoresistance is an important concern in the treatment of metastatic colon cancer. It may emerge through selection of clones that are inherently resistant from the outset or through mechanisms acquired during treatment. Cell fusion represents an efficient means of rapid phenotypic evolution that make cells with new properties at a rate exceeding that achievable by random mutagenesis. Here, we first identified a number of proteins involved in cell fusion using a shotgun proteomics approach, then we investigated the role of these proteins namely tetraspanin CD81/CD9, ADAM10, GTP-binding protein a13, radixin, myosin regulatory light chain and RhoA in the regulation of colon cancer cell fusion. We also found a previously unrecognized role of ADAM10, Ga13 and RhoA in promoting cell fusion. Finally, we show that the occurrence of cell fusion in a metastatic model of colon carcinoma causes the appearance of cells resistant to both 5-fluorouracil and oxaliplatin. These findings highlight the importance of cell fusion in cancer progression and raise significant implications for overcoming chemoresistance in metastatic colon cancer.

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Section: Adam10 and Cd81 Regulate Localization Of Gtp-binding A13mentioning

confidence: 99%

Cell fusion promotes chemoresistance in metastatic colon carcinoma

et al. 2012

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“…The suppressive effect of CT04 on actin aggregation indicates at least partial involvement of Rho activation. Since some Gq coupled receptors have been reported to also interact with G 12/13 signaling [38][39][40][41], it is conceivable that G 12/13 signaling is activated following P2Y 6 receptor stimulation. It was also shown that Rho signaling activated PKCs [18,42,43].…”

Section: Udp-induced Vasp Phosphorylation At Ser157 Is Mediated By Rhmentioning

confidence: 99%

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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“…Both PARs belong to the seven transmembrane family of G-protein linked receptors and have been cloned and sequenced. Both are coupled to Gαq and Gα 12/13 [1]. Thrombin cleaves the receptors within the large N-terminal extracellular domain, creating new amino terminals, SFLLRN and GYPGQV respectively [2,3].…”

Section: Introductionmentioning

confidence: 99%