Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo.
Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo.
复制标题
DOI:
10.1038/srep11789
复制
发表时间:
2015-07-09
影响因子:
4.6
通讯作者:
Klagsbrun M
中科院分区:
文献类型:
--
作者:
Nakayama H;Bruneau S;Kochupurakkal N;Coma S;Briscoe DM;Klagsbrun M
Semaphorin 3F (SEMA3F) provides neuronal guidance cues via its ability to bind neuropilin 2 (NRP2) and Plexin A family molecules. Recent studies indicate that SEMA3F has biological effects in other cell types, however its mechanism(s) of function is poorly understood. Here, we analyze SEMA3F-NRP2 signaling responses in human endothelial, T cell and tumor cells using phosphokinase arrays, immunoprecipitation and Western blot analyses. Consistently, SEMA3F inhibits PI-3K and Akt activity, and responses are associated with the disruption of mTOR/rictor assembly and mTOR-dependent activation of the RhoA GTPase. We also find that the expression of vascular endothelial growth factor, as well as mTOR-inducible cellular activation responses and cytoskeleton stability are inhibited by SEMA3F-NRP2 interactions in vitro. In vivo, local and systemic overproduction of SEMA3F reduces tumor growth in NRP2-expressing xenografts. Taken together, SEMA3F regulates mTOR signaling in diverse human cell types, suggesting that it has broad therapeutic implications.
登录
查看更多内容
影响因子:
11.2
作者:
Kessler, O;Shraga-Heled, N;Neufeld, G
通讯作者:
Neufeld, G
DOI:
10.1126/science.1236566
发表时间:
2013-07-26
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
Kang SA;Pacold ME;Cervantes CL;Lim D;Lou HJ;Ottina K;Gray NS;Turk BE;Yaffe MB;Sabatini DM
通讯作者:
Sabatini DM
影响因子:
11.2
作者:
Cao Y;Hoeppner LH;Bach S;E G;Guo Y;Wang E;Wu J;Cowley MJ;Chang DK;Waddell N;Grimmond SM;Biankin AV;Daly RJ;Zhang X;Mukhopadhyay D
通讯作者:
Mukhopadhyay D
影响因子:
7.5
作者:
Dazert, Eva;Hall, Michael N.
通讯作者:
Hall, Michael N.
影响因子:
4.8
作者:
Gan, Xiaoqing;Wang, Jiyong;Wu, Dianqing
通讯作者:
Wu, Dianqing