Kinase Activation

Lipids and Immunosuppression

Science's STKE  04 Dec 2001:
Vol. 2001, Issue 111, pp. tw449
DOI: 10.1126/stke.2001.111.tw449

Mitogens and other stimuli to cells cause generation of the lipid phosphatidic acid (PA), which acts as a second messenger to promote various cellular responses. Fang et al. identify a new target regulated by PA binding that appears to account for the mitogenic effects of the lipid. In cells treated with PA, the mTOR protein (so named because it is mammalian target of the immunosuppressant rapamycin), which is a phosphatidylinositol kinase-like enzyme, becomes activated. Stimulation of human cells with mitogens increased accumulation of PA and inhibitors of PA production inhibited signaling through mTOR. The results indicate that PA mediates the effects of mitogens to activate mTOR and that rapamycin may interfere with mTOR function by blocking binding of PA.

Y. Fang, M. Vilella-Bach, R. Bachmann, A. Flanigan, J. Chen, Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294, 1942-1945 (2001). [Abstract] [Full Text]