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Cited by 1,367

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism

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Hara, Kenta, Yonezawa, Kazuyoshi, Weng, Qing-Ping, Kozlowski, Mark T., Belham, Christopher, Avruch, Joseph·1998·Journal of Biological Chemistry

Abstract

The present study identifies the operation of a signal tranduction pathway in mammalian cells that provides a checkpoint control, linking amino acid sufficiency to the control of peptide chain initiation. Withdrawal of amino acids from the nutrient medium of CHO-IR cells results in a rapid deactivation of p70 S6 kinase and dephosphorylation of eIF-4E BP1, which become unresponsive to all agonists. Readdition of the amino acid mixture quickly restores the phosphorylation and responsiveness of p70 and eIF-4E BP1 to insulin. Increasing the ambient amino acids to twice that usually employed increases basal p70 activity to the maximal level otherwise attained in the presence of insulin and abrogates further stimulation by insulin. Withdrawal of most individual amino acids also inhibits p70, although with differing potency. Amino acid withdrawal from CHO-IR cells does not significantly alter insulin stimulation of tyrosine phosphorylation, phosphotyrosine-associated phosphatidylinositol 3-kinase activity, c-Akt/protein kinase B activity, or mitogen-activated protein kinase activity. The selective inhibition of p70 and eIF-4E BP1 phosphorylation by amino acid withdrawal resembles the response to rapamycin, which prevents p70 reactivation by amino acids, indicating that mTOR is required for the response to amino acids. A p70 deletion mutant, p70Delta2-46/DeltaCT104, that is resistant to inhibition by rapamycin (but sensitive to wortmannin) is also resistant to inhibition by amino acid withdrawal, indicating that amino acid sufficiency and mTOR signal to p70 through a common effector, which could be mTOR itself, or an mTOR-controlled downstream element, such as a protein phosphatase.

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Metadata

Authors
Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., Belham, C., & Avruch, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1998-06
Volume
273
Issue
23
Pages
14484-14494
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2008239768
Cited by
1,367
References
1
FWCI
16.43
Type
journal article
Language
en
Open access
hybrid

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