Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M112073200 on March 27, 2002

J. Biol. Chem., Vol. 277, Issue 23, 20169-20176, June 7, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/23/20169    most recent
M112073200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vulin, A. I.
Right arrow Articles by Stanley, F. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vulin, A. I.
Right arrow Articles by Stanley, F. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

A Forkhead/Winged Helix-related Transcription Factor Mediates Insulin-increased Plasminogen Activator Inhibitor-1 Gene Transcription*

Anthony Igor Vulin and Frederick M. StanleyDagger

From the Department of Pharmacology, New York University School of Medicine, New York, New York 10016

Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of fibrinolysis by its inhibition of both tissue-type and urokinase plasminogen activators. PAI-1 levels are elevated in type II diabetes and this elevation correlates with macro- and microvascular complications of diabetes. Insulin increases PAI-1 production in several experimental systems, but the mechanism of insulin-activated PAI-1 transcription remains to be determined. Deletion analysis of the PAI-1 promoter revealed that the insulin response element is between -117 and -7. Mutation of the AT-rich site at -52/-45 abolished the insulin responsiveness of the PAI-1 promoter. This sequence is similar to the inhibitory sequence found in the phosphoenolpyruvate carboxylkinase/insulin-like growth factor-I-binding protein I promoters. Gel-mobility shift assays demonstrated that the forkhead bound to the PAI-1 promoter insulin response element. Expression of the DNA-binding domain of FKHR acted as a dominant negative to block insulin-increased PAI-1-CAT expression. A LexA-FKHR construct was also insulin responsive. These data suggested that a member of the Forkhead/winged helix family of transcription factors mediated the effect of insulin on PAI-1 transcription. Inhibition of phosphatidylinositol 3-kinase reduced the effect of insulin on PAI-1 gene expression, a result consistent with activation through FKHR. However, it was likely that a different member of the FKHR family (not FKHR) mediated this effect since FKHR was present in both insulin-responsive and non-responsive cell lines.

* This work was supported by the New York State Health Research Council Diabetes Bridging Grant program and by the National Science Foundation (for support of the Research Computing Resource at the New York University School of Medicine (BIR-9318128)).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Medicine, TCH 450, NYU Medical Center, 550 First Ave., New York, NY 10016. Tel.: 212-263-7927; Fax: 212-263-7701; E-mail: Stanlf01@med.nyu.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Circ. Res.Home page
H. Fujita, M. Kang, M. Eren, L. A. Gleaves, D. E. Vaughan, and T. Kume
Foxc2 Is a Common Mediator of Insulin and Transforming Growth Factor {beta} Signaling to Regulate Plasminogen Activator Inhibitor Type I Gene Expression
Circ. Res., March 17, 2006; 98(5): 626 - 634.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
G. Buchwalter, C. Gross, and B. Wasylyk
The Ternary Complex Factor Net Regulates Cell Migration through Inhibition of PAI-1 Expression
Mol. Cell. Biol., December 15, 2005; 25(24): 10853 - 10862.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. H. Einstein, G. Atzmon, X.-m. Yang, X.-H. Ma, M. Rincon, E. Rudin, R. Muzumdar, and N. Barzilai
Differential Responses of Visceral and Subcutaneous Fat Depots to Nutrients
Diabetes, March 1, 2005; 54(3): 672 - 678.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. K. Ghosh, S. Bhattacharyya, and J. Varga
The Tumor Suppressor p53 Abrogates Smad-dependent Collagen Gene Induction in Mesenchymal Cells
J. Biol. Chem., November 12, 2004; 279(46): 47455 - 47463.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. I. Vulin and F. M. Stanley
Oxidative Stress Activates the Plasminogen Activator Inhibitor Type 1 (PAI-1) Promoter through an AP-1 Response Element and Cooperates with Insulin for Additive Effects on PAI-1 Transcription
J. Biol. Chem., June 11, 2004; 279(24): 25172 - 25178.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement