HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 25, 22586-22595, June 20, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/25/22586    most recent M300705200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ray, A. Articles by Ray, B. K. Search for Related Content PubMed PubMed Citation Articles by Ray, A. Articles by Ray, B. K. Social Bookmarking                      What's this?

Protein Kinase A Signaling Pathway Regulates Transcriptional Activity of SAF-1 by Unmasking Its DNA-binding Domains^*

Alpana Ray , Papiya Ray, Nicole Guthrie, Arvind Shakya, Deepak Kumar and Bimal K. Ray

From the Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri 65211

Serum amyloid A (SAA) activating factor-1 (SAF-1) is an inducible transcription factor that plays a key role in the regulation of several inflammation-responsive genes including SAA and matrix metalloproteinase-1. Increased synthesis of SAA and matrix metalloproteinase-1 is associated with pathogenesis of several diseases including amyloidosis, arthritis, and atherosclerosis. Previously, we showed in vivo interaction of SAF-1 and protein kinase A (PKA) and presented evidence for induction of SAF-1-regulated genes by a PKA signaling pathway. Here we demonstrate a mechanism by which PKA increases functional activities of SAF-1. Site-directed mutagenesis and phosphorylation analyses revealed two sites in the SAF-1 protein, serine 187 and threonine 386, as the target of PKA. Interestingly, mutation of both PKA phosphorylation sites created a highly active SAF-1 protein with high DNA-binding ability. Furthermore, we found that terminal deletion of SAF-1 protein from either end creates SAF-1 isoforms that are highly transcriptionally active. Partial proteolysis experiments indicated that unphosphorylated and phosphorylated SAF-1 proteins are structurally distinct. Together these results suggest that under native condition, N and C termini of SAF-1 are engaged in an inhibitory intramolecular interaction. PKA-mediated phosphorylation increases transcriptional activity of SAF-1 by unmasking the DNA-binding domain.

Received for publication, January 21, 2003 , and in revised form, March 26, 2003.

^* This work was supported by United States Public Health Service Grant DK49205. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 573-882-6728; Fax: 573-884-5414; E-mail: rayal{at}missouri.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Kumar, A. Ray, and B. K. Ray Transcriptional Synergy Mediated by SAF-1 and AP-1: CRITICAL ROLE OF N-TERMINAL POLYALANINE AND TWO ZINC FINGER DOMAINS OF SAF-1 J. Biol. Chem., January 16, 2009; 284(3): 1853 - 1862. [Abstract] [Full Text] [PDF]

				E. Gaillard, N. Bruck, Y. Brelivet, G. Bour, S. Lalevee, A. Bauer, O. Poch, D. Moras, and C. Rochette-Egly Phosphorylation by PKA potentiates retinoic acid receptor {alpha} activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7 PNAS, June 20, 2006; 103(25): 9548 - 9553. [Abstract] [Full Text] [PDF]

				A. Ray, D. Kumar, P. Ray, and B. K. Ray Transcriptional Activity of Serum Amyloid A-activating Factor-1 Is Regulated by Distinct Functional Modules J. Biol. Chem., December 24, 2004; 279(52): 54637 - 54646. [Abstract] [Full Text] [PDF]

				A. Ray, D. Kumar, A. Shakya, C. R. Brown, J. L. Cook, and B. K. Ray Serum Amyloid A-Activating Factor-1 (SAF-1) Transgenic Mice Are Prone to Develop a Severe Form of Inflammation-Induced Arthritis J. Immunol., October 1, 2004; 173(7): 4684 - 4691. [Abstract] [Full Text] [PDF]