Kim, H. W., Ha, S. H., Lee, M. N., Huston, E., Kim, D.-H., Jang, S. K., Suh, P.-G., Houslay, M. D. and Ryu, S. H. (2010) Cyclic AMP Controls mTOR through Regulation of the Dynamic Interaction between Rheb and Phosphodiesterase 4D. Molecular and Cellular Biology, 30(22), pp. 5406-5420. (doi: 10.1128/MCB.00217-10)
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Publisher's URL: http://dx.doi.org/10.1128/MCB.00217-10
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Houslay, Professor Miles and Huston, Dr Elaine |
| Authors: | Kim, H. W., Ha, S. H., Lee, M. N., Huston, E., Kim, D.-H., Jang, S. K., Suh, P.-G., Houslay, M. D., and Ryu, S. H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Molecular and Cellular Biology |
| Publisher: | American Society for Microbiology |
| ISSN: | 0270-7306 |
| ISSN (Online): | 1098-5549 |
| Published Online: | 13 September 2010 |
| Related URLs: |
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