AJP - Lung Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Am J Physiol Lung Cell Mol Physiol 295: L440-L450, 2008. First published June 27, 2008; doi:10.1152/ajplung.00325.2007
1040-0605/08 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
295/3/L440    most recent
00325.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI 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 Google Scholar
Google Scholar
Right arrow Articles by Csortos, C.
Right arrow Articles by Verin, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Csortos, C.
Right arrow Articles by Verin, A. D.

TIMAP is a positive regulator of pulmonary endothelial barrier function

Csilla Csortos,1,* Istvan Czikora,1,* Natalia V. Bogatcheva,3 Djanybek M. Adyshev,2 Christophe Poirier,3 Gabor Olah,2 and Alexander D. Verin3

1Department of Medical Chemistry, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary; 2Department of Medicine, Division of Biological Sciences, University of Chicago, Chicago, Illinois; and 3Medical College of Georgia, Vascular Biology Center, Augusta, Georgia

Submitted 14 August 2007 ; accepted in final form 25 June 2008

TGF-β-inhibited membrane-associated protein, TIMAP, is expressed at high levels in endothelial cells (EC). It is regarded as a member of the MYPT (myosin phosphatase target subunit) family of protein phosphatase 1 (PP1) regulatory subunits; however, its function in EC is not clear. In our pull-down experiments, recombinant TIMAP binds preferentially the β-isoform of the catalytic subunit of PP1 (PP1cβ) from pulmonary artery EC. As PP1cβ, but not PP1c{alpha}, binds with MYPT1 into functional complex, these results suggest that TIMAP is a novel regulatory subunit of myosin phosphatase in EC. TIMAP depletion by small interfering RNA (siRNA) technique attenuates increases in transendothelial electrical resistance induced by EC barrier-protective agents (sphingosine-1-phosphate, ATP) and enhances the effect of barrier-compromising agents (thrombin, nocodazole) demonstrating a barrier-protective role of TIMAP in EC. Immunofluorescent staining revealed colocalization of TIMAP with membrane/cytoskeletal protein, moesin. Moreover, TIMAP coimmunoprecipitates with moesin suggesting the involvement of TIMAP/moesin interaction in TIMAP-mediated EC barrier enhancement. Activation of cAMP/PKA cascade by forskolin, which has a barrier-protective effect against thrombin-induced EC permeability, attenuates thrombin-induced phosphorylation of moesin at the cell periphery of control siRNA-treated EC. On the contrary, in TIMAP-depleted EC, forskolin failed to affect the level of moesin phosphorylation at the cell edges. These results suggest the involvement of TIMAP in PKA-mediated moesin dephosphorylation and the importance of this dephosphorylation in TIMAP-mediated EC barrier protection.

transendothelial electrical resistance; small interfering RNA; moesin interaction with protein phosphatase 1



Address for reprint requests and other correspondence: A. D. Verin, Vascular Biology Center, Medical College of Georgia, CB-3210A, Augusta, GA 30912 (e-mail: averin{at}mcg.edu)




This article has been cited by other articles:


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
X. Guo, L. Wang, B. Chen, Q. Li, J. Wang, M. Zhao, W. Wu, P. Zhu, X. Huang, and Q. Huang
ERM protein moesin is phosphorylated by advanced glycation end products and modulates endothelial permeability
Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H238 - H246.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.