Premium
Role of phospholipase D1 in the regulation of mTOR activity by lysophosphatidic acid
Author(s) -
Kam Yoonseok,
Exton John H.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0731com
Subject(s) - pi3k/akt/mtor pathway , p70 s6 kinase 1 , lysophosphatidic acid , phospholipase d , phosphorylation , phosphatidic acid , protein kinase b , microbiology and biotechnology , pld2 , platelet derived growth factor receptor , ribosomal protein s6 , rptor , chemistry , biology , signal transduction , biochemistry , growth factor , receptor , phospholipid , membrane
Mitogens activate protein translation through phosphorylation of p7S6 kinase (p70 S6K ) and eIF4E binding protein 1 (4E‐BP1) mediated by the mammalian target of rapamycin (mTOR) or phosphoinositide 3‐kinase (PI3K). A recent report ( Science 294, 1942, 2001) has implicated phospholipase D (PLD) in mTOR signaling. We studied the role of PLD in the phosphorylation of p70 S6K and 4E‐BP1 induced by lysophosphatidic acid (LPA) and platelet‐derived growth factor (PDGF) using fibroblasts deficient in PLD activity and also 1‐butanol, which inhibits phosphatidic acid production by PLD. The reduction in PLD activity in both situations impaired the effect of LPA on mTOR signaling but did not inhibit the effect of PDGF. PDGF induced marked phosphorylation of Akt (a PI3K target) but this was not affected by PLD deficiency. LPA caused much less phosphorylation of Akt and this was dependent on PLD activity. Toxin B, which inacti¬vates Rho GTPases, markedly impaired PLD1 activa¬tion and phosphorylation of Akt, p70 S6K , and 4E‐BP1 induced by LPA but had a minimal or no effect on the actions of PDGF. These results support the hypothesis that LPA activates protein translation through the ac¬tion of PLD1‐generated PA on mTOR and the PI3K/ Akt pathway whereas PDGF acts through P13K/Akt independent of PLD1.—Kam, Y., Exton, J. H. Role of phospholipase D1 in the regulation of mTOR activity by lysophosphatidic acid. FASEB J. 18, 311–319 (2004)