Hetero-oligomerization of Rho and Ras GTPases Connects GPCR Activation to mTORC2-AKT Signaling.
Hetero-oligomerization of Rho and Ras GTPases Connects GPCR Activation to mTORC2-AKT Signaling.
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DOI：
10.1016/j.celrep.2020.108427
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发表时间：
2020-11-24
期刊：
影响因子：
8.8
通讯作者：
Iijima M
中科院分区：
文献类型：
--
作者：
Senoo H;Wai M;Matsubayashi HT;Sesaki H;Iijima M
The activation of G-protein-coupled receptors (GPCRs) leads to the activation of mTORC2 in cell migration and metabolism. However, the mechanism that links GPCRs to mTORC2 remains unknown. Here, using Dictyostelium cells, we show that GPCR-mediated chemotactic stimulation induces hetero-oligomerization of phosphorylated GDP-bound Rho GTPase and GTP-bound Ras GTPase in directed cell migration. The Rho-Ras hetero-oligomers directly and specifically stimulate mTORC2 activity toward AKT in cells and after biochemical reconstitution using purified proteins in vitro. The Rho-Ras hetero-oligomers do not activate ERK/MAPK, another kinase that functions downstream of GPCRs and Ras. Human KRas4B functionally replace Dictyostelium Ras in mTORC2 activation. In contrast to GDP-Rho, GTP-Rho antagonizes mTORC2-AKT signaling by inhibiting the oligomerization of GDP-Rho with GTP-Ras. These data reveal that GPCR-stimulated hetero-oligomerization of Rho and Ras provides a critical regulatory step that controls mTORC2-AKT signaling. Senoo et al. report that GPCR-mediated chemotactic stimulation induces hetero-oligomerization of phosphorylated GDP-bound Rho and GTP-bound Ras in cell migration. Rho-Ras hetero-oligomers directly stimulate mTORC2 activity toward AKT in cells and in vitro. Therefore, GPCR-stimulated hetero-oligomerization of Rho and Ras provides a critical regulatory step in mTORC2-AKT signaling.
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影响因子：
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DOI：
10.1073/pnas.1821638116
发表时间：
2019-02-26
影响因子：
11.1
作者：
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通讯作者：
Faix, Jan
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