Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway

Mee Sup Yoon, Guangwei Du, Jonathan M. Backer, Michael A. Frohman, Jie Chen

Research output: Contribution to journalArticle

Abstract

The rapamycin-sensitive mammalian target of rapamycin (mTOR) complex, mTORC1, regulates cell growth in response to mitogenic signals and amino acid availability. Phospholipase D (PLD) and its product, phosphatidic acid, have been established as mediators of mitogenic activation of mTORC1. In this study, we identify a novel role for PLD1 in an amino acid- sensing pathway. We find that amino acids activate PLD1 and that PLD1 is indispensable for amino acid activation of mTORC1. Activation of PLD1 by amino acids requires the class III phosphatidylinositol 3-kinase hVps34, which stimulates PLD1 activity through a functional interaction between phosphatidylinositol 3-phosphate and the Phox homology (PX) domain of PLD1. Furthermore, amino acids stimulate PLD1 translocation to the lysosomal region where mTORC1 activation occurs in an hVps34-dependent manner, and this translocation is necessary for mTORC1 activation. The PX domain is required for PLD1 translocation, mTORC1 activation, and cell size regulation. Finally, we show that the hVps34-PLD1 pathway acts independently of, and in parallel to, the Rag pathway in regulating amino acid activation of mTORC1.

Original languageEnglish (US)
Pages (from-to)435-447
Number of pages13
JournalJournal of Cell Biology
Volume195
Issue number3
DOIs
StatePublished - Oct 31 2011

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Phospholipase D
Phosphatidylinositol 3-Kinases
Amino Acids
Aminoacylation
Sirolimus
Class III Phosphatidylinositol 3-Kinases
Phosphatidic Acids
mechanistic target of rapamycin complex 1
Cell Size
Growth

ASJC Scopus subject areas

  • Cell Biology

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Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway. / Yoon, Mee Sup; Du, Guangwei; Backer, Jonathan M.; Frohman, Michael A.; Chen, Jie.

In: Journal of Cell Biology, Vol. 195, No. 3, 31.10.2011, p. 435-447.

Research output: Contribution to journalArticle

Yoon, Mee Sup ; Du, Guangwei ; Backer, Jonathan M. ; Frohman, Michael A. ; Chen, Jie. / Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway. In: Journal of Cell Biology. 2011 ; Vol. 195, No. 3. pp. 435-447.
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