Differences in Galpha12- and Galpha13-mediated plasma membrane recruitment of p115-RhoGEF.
Differences in Galpha12- and Galpha13-mediated plasma membrane recruitment of p115-RhoGEF.
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DOI：
10.1016/j.cellsig.2009.02.010
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发表时间：
2009-06
影响因子：
4.8
通讯作者：
Wedegaertner PB
中科院分区：
文献类型：
--
作者：
Bhattacharyya R;Banerjee J;Khalili K;Wedegaertner PB
Regulator of G protein signaling domain-containing Rho guanine-nucleotide exchange factors (RGS-RhoGEFs) directly link activated forms of the G12 family of heterotrimeric G protein α subunits to the small GTPase Rho. Stimulation of G12/13-coupled GPCRs or expression of constitutively activated forms of α12 and α13 has been shown to induce the translocation of the RGS-RhoGEF, p115-RhoGEF, from the cytoplasm to the plasma membrane (PM). However, little is known regarding the functional importance and mechanisms of this regulated PM recruitment, and thus PM recruitment of p115-RhoGEF is the focus of this report. A constitutively PM-localized mutant of p115-RhoGEF shows a much greater activity compared to wild type p115-RhoGEF in promoting Rho-dependent neurite retraction of NGF-differentiated PC12 cells, providing the first evidence that PM localization can activate p115-RhoGEF signaling. Next, we uncovered the unexpected finding that Rho is required for α13-induced PM translocation of p115-RhoGEF. However, inhibition of Rho did not prevent α12-induced PM translocation of p115-RhoGEF. Additional differences between α13 and α12 in promoting PM recruitment of p115-RhoGEF were revealed by analyzing RGS domain mutants of p115-RhoGEF. Activated α12 effectively recruits the isolated RGS domain of p115-RhoGEF to the PM, whereas α13 only weakly does. On the other hand, α13 strongly recruits to the PM a p115-RhoGEF mutant containing amino acid substitutions in an acidic region at the N-terminus of the RGS domain; however, α12 is unable to recruit this p115-RhoGEF mutant to the PM. These studies provide new insight into the function and mechanisms of α12/13-mediated PM recruitment of p115-RhoGEF.
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影响因子：
3.5
作者：
Bhattacharyya, R;Wedegaertner, PB
通讯作者：
Wedegaertner, PB
影响因子：
4
作者：
Meyer, Bruno H.;Freuler, Felix;Siehler, Sandra
通讯作者：
Siehler, Sandra
影响因子：
5.3
作者：
Apolloni, A;Prior, IA;Hancock, JF
通讯作者：
Hancock, JF
影响因子：
4.8
作者：
Kreutz, Barry;Hajicek, Nicole;Kozasa, Tohru
通讯作者：
Kozasa, Tohru
影响因子：
4.8
作者：
Katoh, H;Aoki, J;Negishi, M
通讯作者：
Negishi, M