HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/5/E964    most recent 00239.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Faridi, J. Articles by Roth, R. A. Search for Related Content PubMed PubMed Citation Articles by Faridi, J. Articles by Roth, R. A.

Akt promotes increased mammalian cell size by stimulating protein synthesis and inhibiting protein degradation

¹Department of Molecular Pharmacology, Stanford University, Stanford, California 94305; ²Section of Endocrinology, Veterans Affairs Medical Center, Phoenix 85012; and ³Department of Molecular and Cellular Biology, Arizona State University, Tempe, Arizona 85287

Submitted 23 May 2003 ; accepted in final form 14 July 2003

Expression of constitutively active Akt3 was found to increase the size of MCF-7 cells approximately twofold both in vitro and in vivo. A regulatable version of Akt1 (MER-Akt) was also found capable of inducing a twofold increase in the size of H4IIE rat hepatoma cells. Rapamycin, a specific inhibitor of mTOR function, was found to inhibit the Akt-induced increase in cell size by 70%, presumably via inhibition of the Akt-induced increase in protein synthesis. To determine whether Akt could be inhibiting protein degradation, thereby contributing to its ability to induce an increase in cell size, we conducted protein degradation experiments in the H4IIE cell line. Activation of MER-Akt was found to inhibit protein degradation to a degree comparable to insulin treatment. The effects of these two agents on protein degradation were not additive, thereby suggesting that they were acting on a similar pathway. An inhibitor of the phosphatidylinositol 3-kinase pathway, LY-294002, blocked both insulin- and Akt-induced inhibition of protein degradation, again consistent with the hypothesis that both agents were acting on the same pathway. In contrast, rapamycin did not block the ability of either agent to inhibit protein degradation. These results indicate that Akt increases cell size through both mTOR-dependent and -independent pathways and that the latter involves inhibition of protein degradation. These studies are also consistent with the hypothesis that insulin's ability to regulate protein degradation is to a large extent mediated via Akt.

cell growth; protein kinase B; mammalian target of rapamycin; rapamycin

This article has been cited by other articles:

				E. E. Dupont-Versteegden, B. A. Strotman, C. M. Gurley, D. Gaddy, M. Knox, J. D. Fluckey, and C. A. Peterson Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1730 - R1740. [Abstract] [Full Text] [PDF]

				B. DeBosch, I. Treskov, T. S. Lupu, C. Weinheimer, A. Kovacs, M. Courtois, and A. J. Muslin Akt1 Is Required for Physiological Cardiac Growth Circulation, May 2, 2006; 113(17): 2097 - 2104. [Abstract] [Full Text] [PDF]

				J. M. McClung, R. W. Thompson, L. L. Lowe, and J. A. Carson RhoA expression during recovery from skeletal muscle disuse J Appl Physiol, April 1, 2004; 96(4): 1341 - 1348. [Abstract] [Full Text] [PDF]

				K. L. Hoehn, S. F. Hudachek, S. A. Summers, and G. L. Florant Seasonal, tissue-specific regulation of Akt/protein kinase B and glycogen synthase in hibernators Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2004; 286(3): R498 - R504. [Abstract] [Full Text] [PDF]