This Article Full Text Full Text (PDF) All Versions of this Article: 18/4/1033    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guo, Y. Articles by Siddiqui, M. A. Q. Search for Related Content PubMed PubMed Citation Articles by Guo, Y. Articles by Siddiqui, M. A. Q.

Distinct Components of Janus Kinase/Signal Transducer and Activator of Transcription Signaling Pathway Mediate the Regulation of Systemic and Tissue Localized Renin-Angiotensin System

Center for Cardiovascular and Muscle Research and Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203

Address all correspondence and requests for reprints to: M.A.Q. Siddiqui, Department of Anatomy and Cell Biology, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203. E-mail: MAQ.Siddiqui{at}downstate.edu.

In an attempt to demonstrate the linkage between the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) signaling and the activity of the systemic or local renin-angiotensin system in vivo, we produced transgenic mice harboring angiotensinogen (ANG) promoter containing the wild-type or mutant STAT target site (St-domain) fused to the luciferase reporter. The ANG-promoter-driven luciferase expression was dependent upon phosphorylation of Jak2, as administration of tyrphostin AG490, a potent inhibitor of Jak2, down-regulated the ANG promoter activity and abolished the stimulated endogenous ANG mRNA level in the liver. Administration of angiotensin II peptide to the mice resulted in prominent expression of luciferase in the liver and heart of animals containing wild type St-domain, but not in transgenes with mutant St-domain. Angiotensin II-induced signaling caused activation of STAT proteins in the liver (systemic), the pattern of which was distinct from that in the heart (local). The inducible expression of ANG promoter appears to be mediated by physical association of p300 with STAT 5B in liver and STAT 3 and STAT 5A in heart. Taken together, these results point to the differences in signaling mechanisms in the circulating and localized renin-angiotensin system and identify at least two molecular steps, the tyrosyl phosphorylation of Jak2 and the STAT/St-domain interaction, as pivotal in the regulation of ANG gene transcription.

This article has been cited by other articles:

				J. Espinoza-Derout, M. Wagner, K. Shahmiri, E. Mascareno, B. Chaqour, and M.A.Q. Siddiqui Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy Cardiovasc Res, July 1, 2007; 75(1): 129 - 138. [Abstract] [Full Text] [PDF]

				K. E. Jie, M. C. Verhaar, M.-J. M. Cramer, K. van der Putten, C. A. J. M. Gaillard, P. A. Doevendans, H. A. Koomans, J. A. Joles, and B. Braam Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors Am J Physiol Renal Physiol, November 1, 2006; 291(5): F932 - F944. [Abstract] [Full Text] [PDF]

				P. Blancafort, E. I. Chen, B. Gonzalez, S. Bergquist, A. Zijlstra, D. Guthy, A. Brachat, R. H. Brakenhoff, J. P. Quigley, D. Erdmann, et al. Genetic reprogramming of tumor cells by zinc finger transcription factors PNAS, August 16, 2005; 102(33): 11716 - 11721. [Abstract] [Full Text] [PDF]