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        Activation of Small GTPases RhoA and Rac1 Is Required for Avian Reovirus p10-induced Syncytium Formation

        Hung-Jen Liu,Ping-Yuan Lin,Ling-Rung Wang,Hsue-Yin Hsu,Ming-Huei Liao,Wen-Ling Shih 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.4

        The first ORF of the ARV S1133 S1 segment encodes the nonstructural protein p10, which is responsible for the induction of cell syncytium formation. However, p10-dependent signaling during syncytium formation is fully unknown. Here, we show that dominant negative RhoA, Rho inhibitor C3 exoenzyme, ROCK/Rho-kinase inhibitor Y-27632 and Rac1 inhibitor NSC23766 inhibit p10-mediated cell fusion. p10 over-expression is concomitant with activation and membrane translocation of RhoA and Rac1, but not cdc42. RhoA and Rac1 downstream events, including JNK phosphorylation and transcription factor AP-1 and NF-B activation, as well as MLC expression and phosphorylation are simultaneously activated by p10. p10 point mutant T13M possessed 20% fusion-inducing ability and four p10 fusion-deficient mutants V15M, V19M, C21S and L32A reduced or lost their ability to activate RhoA and Rac1 signaling. We conclude that p10-mediated syncytium formation proceeds by utilizing RhoA and Rac1-dependent signaling.

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