CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leicht, M.
Right arrow Articles by Hoppe, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leicht, M.
Right arrow Articles by Hoppe, J.

Cell Growth & Differentiation, Vol 7, Issue 9 1199-1209, Copyright © 1996 by American Association of Cancer Research


ARTICLES

Okadaic acid induces cellular hypertrophy in AKR-2B fibroblasts: involvement of the p70S6 kinase in the onset of protein and rRNA synthesis

M Leicht, A Simm, G Bertsch and J Hoppe
Theodor-Boveri-Institut fur Biowissenschaften (Biozentrum), Universitat, Wurzburg, Germany.

At low concentrations (50 nM), okadaic acid (OA), an inhibitor of phosphatases 1 and 2A, inhibits platelet-derived growth factor-induced cell proliferation in late G1 (A. Simm et al., Exp. Cell Res., 210: 160-165, 1994). This inhibition is caused by the interference of OA in the induction and activation of the cell division protein kinases cdk1 and cdk2. OA alone has no effect on cell number, but induces a pronounced increase in cell size. The OA-induced hypertrophy can be divided into two phases. The first phase is characterized by a swelling of the cells. This increase in cellular volume is not accompanied by a change in the level of cellular macromolecules, i.e., protein and RNA. Inhibitor studies indicated a possible role of the Na+/H+ antiporter and Cl- channels in this process. In the second phase, an increase in the cellular protein and RNA content was observed along with a minor change in cell volume. To delineate a possible signaling pathway, the involvement of numerous protein kinases was analyzed. Low concentrations of OA lead to pronounced and sustained activation of the p70S6 kinase. There was little or no effect on various other kinases that can be activated by extracellular signals, e.g., mitogen-activated kinase, ribosomal S6 kinase, or other S6 peptide kinases. Likewise, at these concentrations, OA did not activate the genes for fos, myc, or ornithine decarboxylase. At very low concentrations (ED50, 0.5 nM), rapamycin, a specific inhibitor of the activation of p70S6 kinase, reversed the activation of the p70S6 kinase and the enhancement of RNA synthesis and partially the increase in cell volume and protein synthesis. The OA-induced hypertrophy of AKR-2B fibroblasts may serve as a model system for investigations aimed at the identification of signaling pathways leading to hypertrophy of differentiated nonproliferating cells.


This article has been cited by other articles:


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Liangpunsakul, Y. Rahmini, R. A. Ross, Z. Zhao, Y. Xu, and D. W. Crabb
Imipramine blocks ethanol-induced ASMase activation, ceramide generation, and PP2A activation, and ameliorates hepatic steatosis in ethanol-fed mice
Am J Physiol Gastrointest Liver Physiol, March 1, 2012; 302(5): G515 - G523.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
E. Liu, C. A. Knutzen, S. Krauss, S. Schweiger, and G. G. Chiang
Control of mTORC1 signaling by the Opitz syndrome protein MID1
PNAS, May 24, 2011; 108(21): 8680 - 8685.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
V. K. Anagnostou, G. Bepler, K. N. Syrigos, L. Tanoue, S. Gettinger, R. J. Homer, D. Boffa, F. Detterbeck, and D. L. Rimm
High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma
Clin. Cancer Res., June 15, 2009; 15(12): 4157 - 4164.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
K. D. Cygnar, X. Gao, D. Pan, and T. P. Neufeld
The Phosphatase Subunit Tap42 Functions Independently of Target of Rapamycin to Regulate Cell Division and Survival in Drosophila
Genetics, June 1, 2005; 170(2): 733 - 740.
[Abstract] [Full Text] [PDF]


Home page
Microbiol. Mol. Biol. Rev.Home page
K. Inoki, H. Ouyang, Y. Li, and K.-L. Guan
Signaling by Target of Rapamycin Proteins in Cell Growth Control
Microbiol. Mol. Biol. Rev., March 1, 2005; 69(1): 79 - 100.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. J. James and J. C. B. M. Zomerdijk
Phosphatidylinositol 3-Kinase and mTOR Signaling Pathways Regulate RNA Polymerase I Transcription in Response to IGF-1 and Nutrients
J. Biol. Chem., March 5, 2004; 279(10): 8911 - 8918.
[Abstract] [Full Text] [PDF]


Home page
EMBO J.Home page
C. K. Tsang, P. G. Bertram, W. Ai, R. Drenan, and X. F. S. Zheng
Chromatin-mediated regulation of nucleolar structure and RNA Pol I localization by TOR
EMBO J., November 17, 2003; 22(22): 6045 - 6056.
[Abstract] [Full Text] [PDF]


Home page
Microbiol. Mol. Biol. Rev.Home page
J. L. Crespo and M. N. Hall
Elucidating TOR Signaling and Rapamycin Action: Lessons from Saccharomyces cerevisiae
Microbiol. Mol. Biol. Rev., December 1, 2002; 66(4): 579 - 591.
[Abstract] [Full Text] [PDF]


Home page
Sci SignalHome page
J. Montagne, T. Radimerski, and G. Thomas
Insulin Signaling: Lessons from the Drosophila Tuberous Sclerosis Complex, a Tumor Suppressor
Sci. Signal., October 23, 2001; 2001(105): pe36 - pe36.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
B. Raught, A.-C. Gingras, and N. Sonenberg
The target of rapamycin (TOR) proteins
PNAS, June 19, 2001; 98(13): 7037 - 7044.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
T. Powers and P. Walter
Regulation of Ribosome Biogenesis by the Rapamycin-sensitive TOR-signaling Pathway in Saccharomyces cerevisiae
Mol. Biol. Cell, April 1, 1999; 10(4): 987 - 1000.
[Abstract] [Full Text]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1996 by the American Association of Cancer Research.