What question did this study set out to answer?

To determine the molecular mechanisms by which amino acid availability signals to activate the mTORC1 growth-regulatory protein kinase complex.

May 22, 2008Science

The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

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Authors

YSYasemin SancakUniversity of Washington TPTimothy R. PetersonTechnologies pour la Santé YSYoav D. ShaulHebrew College

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Implication

Cellular study demonstrates that Rag GTPases mediate amino acid activation of mTORC1 by directing its intracellular localization to Rheb, highlighting a key mechanism in metabolic control.

Key Points

To determine the molecular mechanisms by which amino acid availability signals to activate the mTORC1 growth-regulatory protein kinase complex.
Assessed physical interactions between Rag GTPase family members and mTORC1 under amino acid-rich and amino acid-depleted conditions.
Engineered and expressed constitutively GTP-bound and GDP-bound Rag mutants in cells to evaluate mTORC1 pathway activity.
Analyzed the intracellular spatial trafficking and localization of mTOR relative to its activator Rheb.
Rag GTPases interacted with mTORC1 in an amino acid-sensitive manner and were essential for amino acid-dependent activation of the pathway.
Expression of constitutively active GTP-bound Rag rendered mTORC1 resistant to amino acid deprivation, whereas GDP-bound Rag blocked amino acid activation.
Rag proteins did not alter intrinsic kinase activity directly, but instead directed the intracellular localization of mTOR to a compartment containing Rheb.

Cite This Study

Sancak et al. (2008) studied this question.

synapsesocial.com/papers/69dd3f31fb7610310c101425 https://doi.org/10.1126/science.1157535

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Implication

Cellular study demonstrates that Rag GTPases mediate amino acid activation of mTORC1 by directing its intracellular localization to Rheb, highlighting a key mechanism in metabolic control.

The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

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Member takes

Implication

Key Points

Cite This Study

The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

Discussion

Member takes

Implication

Key Points

Cite This Study

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