Biochemical and Biophysical Research Communications
mTORC2 regulates PGE2-mediated endothelial cell survival and migration
Section snippets
Materials and methods
Reagents and plasmids. Rapamycin was from Calbiochem. Antibodies used for Western blot were anti-phospho-Ser473 Akt, Akt, anti phospho-Thr-389-S6K1, S6K1, raptor, rictor, and actin all purchased from Cell Signaling Technologies. Anti Rac antibody was from Sigma. PGE2 was from Biomol. The dominant negative mutant of Rac was as described previously [5].
Cell culture. Human umbilical vein endothelial cells were prepared and cultured as previously described [19] in M199 (Cambrex) supplemented with
PGE2 activates mTORC1 and mTORC2 in EC
To investigate the function of mTOR signaling pathway in PGE2-induced EC responses, we first evaluated the ability of PGE2 to activate mTORC1 and mTORC2 in EC. To investigate this, EC were stimulated for different period of time with PGE2 and the phosphorylation of S6K1 and Akt, two well-established downstream targets of mTORC1 and mTORC2, respectively [12], [15], was analyzed by Western blot. We found that PGE2-induced both S6K1 and Akt phosphorylation. The effect was apparent after 15 min
Discussion
PGE2 regulates tumor angiogenesis by in part promoting EC survival and by increasing EC migration. The signaling molecules implicated in these processes have however not been fully characterized. In this study, we have analyzed the role of mTORC1 and mTORC2 in PGE2-mediated EC responses. Our findings were that PGE2 activates both complexes in EC and that mTORC2 is an important signaling intermediary in PGE2-mediated EC survival and migration.
EC survival is critical for the formation and the
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