Gene interactions and pathways from curated databases and text-mining
Cancer Res 2007, PMID: 17210675

Regulation of mTOR by phosphatidic acid?

Foster, David A

Interest in the regulation of the mammalian target of rapamycin (mTOR) has increased substantially in recent years largely because of an apparent link between mTOR and survival signals in human cancer cells. Much has been learned about the regulation of mTOR in response to survival signals generated by phosphatidylinositol 3-kinase (PI3K). However, another mechanism for regulating mTOR has been proposed involving the generation of phosphatidic acid (PA). PA is the metabolic product of phospholipase D (PLD), whose activity is elevated in a large number of human cancers, and, like PI3K, has been implicated in the survival of human cancer cells. Although the regulation of mTOR by the PI3K signaling pathway is well established, a role for PLD and PA in regulating mTOR has been controversial. In this review, the evidence implicating PLD and PA in the regulation of mTOR is summarized, and the implications of this novel and potentially important mechanism for regulating mTOR are discussed.

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Text Mining Data

mTOR → PLD: " Although the regulation of mTOR by the PI3K signaling pathway is well established, a role for PLD and PA in regulating mTOR has been controversial "

mTOR — PLD: " In this review, the evidence implicating PLD and PA in the regulation of mTOR is summarized, and the implications of this novel and potentially important mechanism for regulating mTOR are discussed "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: TSC2 → STK11 (increases, STK11 Activity, TSC2 Activity)
    Evidence: TSC1/2 can also be targeted and activated by LKB1 tumor suppressor protein, activating the AMPdependent kinase
  • OpenBEL Selventa BEL large corpus: O/5 complex () → HRAS (increases, HRAS Activity, Activity)
    Evidence: Elevated PLD activity, under most circumstances, does not lead to increased phosphorylation of Akt. Increased expression of PLD1 led to increased S6 kinase phosphorylation but did not increase Akt phosphorylation in rat fibroblasts (16). However, PLD1-induced increases in S6 kinase phosphorylation were blocked by the PI3K inhibitor LY294002 (16). Similarly, LY294002 suppressed S6 kinase phosphorylation in MDA-MB-231 cells, where there is elevated expression of PLD1 and elevated PLD activity (15)...