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Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

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Cyclic AMP Controls mTOR through Regulation of the Dynamic Interaction between Rheb and Phosphodiesterase 4D

Cited 17 times inthomson ciCited 15 times inthomson ci
Title
Cyclic AMP Controls mTOR through Regulation of the Dynamic Interaction between Rheb and Phosphodiesterase 4D
Author
Kim, Hyun WookHa, Sang HoonLee, Mi NamHuston, ElaineKim, Do-HyungJang, Sung KeySuh, Pann-GhillHouslay, Miles D.Ryu, Sung Ho
Issue Date
2010-11
Publisher
AMER SOC MICROBIOLOGY
Citation
MOLECULAR AND CELLULAR BIOLOGY, v.30, no.22, pp.5406 - 5420
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is a molecular hub that regulates protein synthesis in response to a number of extracellular stimuli. Cyclic AMP (cAMP) is considered to be an important second messenger that controls mTOR; however, the signaling components of this pathway have not yet been elucidated. Here, we identify cAMP phosphodiesterase 4D (PDE4D) as a binding partner of Rheb that acts as a cAMP-specific negative regulator of mTORC1. Under basal conditions, PDE4D binds Rheb in a noncatalytic manner that does not require its cAMP-hydrolyzing activity and thereby inhibits the ability of Rheb to activate mTORC1. However, elevated cAMP levels disrupt the interaction of PDE4D with Rheb and increase the interaction between Rheb and mTOR. This enhanced Rheb-mTOR interaction induces the activation of mTORC1 and cap-dependent translation, a cellular function of mTORC1. Taken together, our results suggest a novel regulatory mechanism for mTORC1 in which the cAMP-determined dynamic interaction between Rheb and PDE4D provides a key, unique regulatory event. We also propose a new role for PDE4 as a molecular transducer for cAMP signaling.
URI
https://scholarworks.unist.ac.kr/handle/201301/8999
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78649567118
DOI
10.1128/MCB.00217-10
ISSN
0270-7306
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BIO_Journal Papers
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