DOI: 10.1073/pnas.95.4.1432. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1

RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1

10.1073/pnas.95.4.1432

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The complex of rapamycin with its intracellular receptor, FKBP12, interacts with RAFT1/FRAP/mTOR, the in vivo rapamycin-sensitive target and a member of the ataxia telangiectasia mutated (ATM)-related family of kinases that share homology with the catalytic domain of phosphatidylinositol 3-kinase. The function of RAFT1 in the rapamycin-sensitive pathway and its connection to downstream components of the pathway, such as p70 S6 kinase and 4E-BP1, are poorly understood. Here, we show that RAFT1 directly phosphorylates p70 S6k , 4E-BP1, and 4E-BP2 and that serum stimulates RAFT1 kinase activity with kinetics similar to those of p70 S6k and 4E-BP1 phosphorylation. RAFT1 phosphorylates p70 S6k on Thr-389, a residue whose phosphorylation is rapamycin-sensitive in vivo and necessary for S6 kinase activity. RAFT1 phosphorylation of 4E-BP1 on Thr-36 and Thr-45 blocks its association with the cap-binding protein, eIF-4E, in vitro , and phosphorylation of Thr-45 seems to be the major regulator of the 4E-BP1–eIF-4E interaction in vivo . RAFT1 phosphorylates p70 S6k much more effectively than 4E-BP1, and the phosphorylation sites on the two proteins show little homology. This raises the possibility that, in vivo , an unidentified kinase analogous to p70 S6k is activated by RAFT1 phosphorylation and acts at the rapamycin-sensitive phosphorylation sites of 4E-BP1.

Bibliography

Burnett, P. E., Barrow, R. K., Cohen, N. A., Snyder, S. H., & Sabatini, D. M. (1998). RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proceedings of the National Academy of Sciences, 95(4), 1432â1437.

Authors 5

Patrick E. Burnett (first)
Roxanne K. Barrow (additional)
Noam A. Cohen (additional)
Solomon H. Snyder (additional)
David M. Sabatini (additional)

References 35 Referenced 948

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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:52 p.m.)
Indexed	1 month ago (July 26, 2025, 4:57 a.m.)
Issued	27 years, 6 months ago (Feb. 17, 1998)
Published	27 years, 6 months ago (Feb. 17, 1998)
Published Online	27 years, 6 months ago (Feb. 17, 1998)
Published Print	27 years, 6 months ago (Feb. 17, 1998)

Funders 0

None

BibTeX

@article{Burnett_1998, title={RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.4.1432}, DOI={10.1073/pnas.95.4.1432}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Burnett, Patrick E. and Barrow, Roxanne K. and Cohen, Noam A. and Snyder, Solomon H. and Sabatini, David M.}, year={1998}, month=feb, pages={1432–1437} }

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