Am J Physiol Cell Physiol Journal of Neurophysiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (March 24, 2004). doi:10.1152/ajpcell.00534.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/2/C310    most recent
00534.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sans, M. D.
Right arrow Articles by Williams, J. A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sans, M. D.
Right arrow Articles by Williams, J. A
Submitted on December 1, 2003
Accepted on March 22, 2004

Calcineurin is required for translational control of protein synthesis in rat pancreatic acini

Maria Dolors Sans1* and John A Williams1

1 Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA

* To whom correspondence should be addressed. E-mail: mdsansg{at}umich.edu.

Cholecystokinin (CCK) increases the rate of net protein synthesis in rat pancreatic acini by activating initiation and elongation factors required for translation. The immunosupressant FK506 inhibits the Ca2+/calmodulin-dependent phosphatase calcineurin in pancreatic acinar cells and blocks pancreatic growth induced by chronic CCK treatment. To test a requirement for calcineurin in the activation of the translational machinery stimulated by CCK we evaluated the effects of FK506 on protein synthesis and on regulatory initiation and elongation factors in rat pancreatic acini in vitro. CCK acutely increased protein synthesis in acini from normal rats with a maximum increase at 100 pM CCK to 170 ± 11 % of control. The immunosupressant FK506 dose-dependently inhibited CCK-stimulated protein synthesis over the same concentration range that blocked calcineurin activity as assessed by dephosphorylation of the calcineurin substrate CRHSP-24. Another immunosupressant, cyclosporine A inhibited protein synthesis but its effects appeared more complex. FK506 also inhibited protein synthesis stimulated by bombesin and carbachol. FK506 did not significantly affect the activity of the initiation factor-2B, or the phosphorylation of the initiation factor-2{alpha}, ribosomal protein protein S6 or the mRNA cap binding protein eIF4E. Instead, blockade of calcineurin with FK506 reduced the phosphorylation of the eIF4E binding protein, reduced the formation of the eIF4F complex and increased the phosphorylation of eEF2. From these results we conclude that calcineurin activity is required for protein synthesis, and this action may be related to an effect on the formation of the mRNA cap binding complex and the elongation processes.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. U. Shah, A. Sarwar, A. I. Orabi, S. Gautam, W. M. Grant, A. J. Park, A. U. Shah, J. Liu, P. K. Mistry, D. Jain, et al.
Protease activation during in vivo pancreatitis is dependent on calcineurin activation
Am J Physiol Gastrointest Liver Physiol, November 1, 2009; 297(5): G967 - G973.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. J. Crozier, M. D. Sans, C. H. Lang, L. G. D'Alecy, S. A. Ernst, and J. A. Williams
CCK-induced pancreatic growth is not limited by mitogenic capacity in mice
Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1148 - G1157.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
G. T. Gurda, L. Guo, S.-H. Lee, J. D. Molkentin, and J. A. Williams
Cholecystokinin Activates Pancreatic Calcineurin-NFAT Signaling In Vitro and In Vivo
Mol. Biol. Cell, January 1, 2008; 19(1): 198 - 206.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Z. Husain, W. M. Grant, F. S. Gorelick, M. H. Nathanson, and A. U. Shah
Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin
Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1594 - G1599.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.