Modification of p115RhoGEF Ser(330) regulates its RhoGEF activity.

Modification of p115RhoGEF Ser(330) regulates its RhoGEF activity.
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DOI:
10.1016/j.cellsig.2013.06.012
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发表时间:
2013-11
影响因子:
4.8
通讯作者:
Kozasa T
Kozasa T
中科院分区:
生物学2区
文献类型:
--
作者:
Chow CR;Suzuki N;Kawamura T;Hamakubo T;Kozasa T

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p115RhoGEF is a member of a family of Rho-specific guanine nucleotide exchange factors that also contains a regulator of G protein signaling homology domain (RH-RhoGEFs) that serves as a link between Gα13 signaling and RhoA activation. While the mechanism of regulation of p115RhoGEF by Gα13 is becoming well-known, the role of other regulatory mechanisms, such as post-translational modification or autoinhibition, in mediating p115RhoGEF activity are less well-characterized. Here, putative phosphorylation sites on p115RhoGEF are identified and characterized. Mutation of Ser330 leads to a decrease in serum response element-mediated transcription as well as decreased activation by Gα13 in vitro. Additionally, this study provides the first report of the binding kinetics between full-length p115RhoGEF and RhoA in its various nucleotide states and examines the binding kinetics of phospho-mutant p115RhoGEF to RhoA. These data, together with other recent reports on regulatory mechanisms of p115RhoGEF, suggest that this putative phosphorylation site serves as a means for initiation or relief of autoinhibition of p115RhoGEF, providing further insight into the regulation of its activity.
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