Mammalian target of rapamycin ( mTOR ) complex 2 regulates filamin A‐dependent focal adhesion dynamics and cell migration

The serine/threonine kinase mTOR forms two distinct complexes, mTORC 1 and mTORC 2, and controls a number of biological processes, including proliferation, survival and autophagy. Although the function of mTORC 1 has been extensively studied, the mTORC 2 signaling pathway largely remains to be elucidated. Here, we have shown that mTORC 2 phosphorylates filamin A, an actin cross‐linking protein, at serine 2152 (S2152) both in vivo and in living cells. Treatment of HeLa cells with Torin1 (an mTORC 1/ mTORC 2 inhibitor), but not rapamycin (an mTORC 1 inhibitor), suppressed the phosphorylation of filamin A, which decreased the binding of filamin A with β7‐integrin cytoplasmic tail. Torin1 also inhibited focal adhesion formation and cell migration in A7 filamin A‐replete melanoma cells but not in M2 filamin A‐deficient cells, suggesting a pivotal role for mTORC 2 in filamin A function. Finally, reduced focal adhesion formation in M2 cells was significantly rescued by expressing wild type but not S2152A nonphosphorylatable mutant of filamin A. Taken together, our results indicate that mTORC 2 regulates filamin A‐dependent focal adhesions and cell migration.