| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print May 19, 2005
Laboratory of Cellular and Molecular Biology, NIH, Baltimore, Maryland 21224
Corresponding Author: morinp{at}grc.nia.nih.gov
Claudins are integral membrane proteins essential in the formation and function of tight junctions (TJs). Disruption of TJs, which have essential roles in cell permeability and polarity, is thought to contribute to epithelial tumorigenesis. Claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer, but the molecular pathways involved in the regulation of these proteins are unclear. Interestingly, several studies have demonstrated a role for phosphorylation in the regulation of TJ complexes, although evidence for claudin phosphorylation is scarce. Here, we show that claudin-3 and claudin-4 can be phosphorylated in ovarian cancer cells. In vitro phosphorylation assays using GST fusion constructs demonstrate that the C-terminus of claudin-3 is an excellent substrate for cAMP-dependent protein kinase (PKA). Using site-directed mutagenesis, we have identified a PKA phosphorylation site at amino acid 192 in the C-terminus of claudin-3. Overexpression of the protein containing a T192D mutation, mimicking the phosphorylated state, results in a decrease in TJ strength in ovarian cancer cell line OVCA433. Our results suggests that claudin-3 phosphorylation by PKA, a kinase frequently activated in ovarian cancer, may provide a mechanism for the disruption of TJs in this cancer. In addition, our findings may have general implications for the regulation of TJs in normal epithelial cells.
J. Biol. Chem, 10.1074/jbc.M502003200
Submitted on February 22, 2005
Accepted on May 19, 2005
Phosphorylation of claudin-3 at threonine 192 by PKA regulates tight junction barrier function in ovarian cancer cells
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V. P. Pai and N. D. Horseman Biphasic Regulation of Mammary Epithelial Resistance by Serotonin through Activation of Multiple Pathways J. Biol. Chem., November 7, 2008; 283(45): 30901 - 30910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Angelow, R. Ahlstrom, and A. S. L. Yu Biology of claudins Am J Physiol Renal Physiol, October 1, 2008; 295(4): F867 - F876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Farquhar, H. J. Harris, M. Diskar, S. Jones, C. J. Mee, S. U. Nielsen, C. L. Brimacombe, S. Molina, G. L. Toms, P. Maurel, et al. Protein Kinase A-Dependent Step(s) in Hepatitis C Virus Entry and Infectivity J. Virol., September 1, 2008; 82(17): 8797 - 8811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sabath, H. Negoro, S. Beaudry, M. Paniagua, S. Angelow, J. Shah, N. Grammatikakis, A. S. L. Yu, and B. M. Denker G{alpha}12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly J. Cell Sci., March 15, 2008; 121(6): 814 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Tipsmark, D. A. Baltzegar, O. Ozden, B. J. Grubb, and R. J. Borski Salinity regulates claudin mRNA and protein expression in the teleost gill Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R1004 - R1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lioni, P. Brafford, C. Andl, A. Rustgi, W. El-Deiry, M. Herlyn, and K. S.M. Smalley Dysregulation of Claudin-7 Leads to Loss of E-Cadherin Expression and the Increased Invasion of Esophageal Squamous Cell Carcinoma Cells Am. J. Pathol., February 1, 2007; 170(2): 709 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Zeissig, N Burgel, D Gunzel, J Richter, J Mankertz, U Wahnschaffe, A J Kroesen, M Zeitz, M Fromm, and J-D Schulzke Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease Gut, January 1, 2007; 56(1): 61 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Honda, M. J. Pazin, H. Ji, R. P. Wernyj, and P. J. Morin Crucial Roles of Sp1 and Epigenetic Modifications in the Regulation of the CLDN4 Promoter in Ovarian Cancer Cells J. Biol. Chem., July 28, 2006; 281(30): 21433 - 21444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ikari, S. Matsumoto, H. Harada, K. Takagi, H. Hayashi, Y. Suzuki, M. Degawa, and M. Miwa Phosphorylation of paracellin-1 at Ser217 by protein kinase A is essential for localization in tight junctions J. Cell Sci., May 1, 2006; 119(9): 1781 - 1789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Le Moellic, S. Boulkroun, D. Gonzalez-Nunez, I. Dublineau, F. Cluzeaud, M. Fay, M. Blot-Chabaud, and N. Farman Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1513 - C1521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Morin Claudin Proteins in Human Cancer: Promising New Targets for Diagnosis and Therapy Cancer Res., November 1, 2005; 65(21): 9603 - 9606. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
