Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor

Joseph Avruch*, Xiaomeng Long, Yenshou Lin, Sara Ortiz-Vega, Joseph Rapley, Angela Papageorgiou, Noriko Oshiro, Ushio Kikkawa

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

52 引文 斯高帕斯(Scopus)

摘要

The signalling function of mTOR complex 1 is activated by Rheb-GTP, which controls the catalytic competence of the mTOR (mammalian target of rapamycin) kinase domain by an incompletely understood mechanism. Rheb can bind directly to the mTOR kinase domain, and association with inactive nucleotide-deficient Rheb mutants traps mTOR in a catalytically inactive state. Nevertheless, Rheb-GTP targets other than mTOR, such as FKBP38 (FK506-binding protein 38) and/or PLD1 (phospholipase D1), may also contribute to mTOR activation. Once activated, the mTOR catalytic domain phosphorylates substrates only when they are bound to raptor (regulatory associated protein of mTOR), a separate polypeptide within the complex. The mechanism of insulin/nutrient stimulation of mTOR complex 1 signalling, in addition to Rheb-GTP activation of the mTOR catalytic function, also involves a stable modification of the configuration of mTORC1 (mTOR complex 1) that increases access of substrates to their binding site on the raptor polypeptide. The mechanism underlying this second step in the activation of mTORC1 is unknown.

原文英語
頁(從 - 到)223-226
頁數4
期刊Biochemical Society Transactions
37
發行號1
DOIs
出版狀態已發佈 - 2009

ASJC Scopus subject areas

  • 生物化學

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