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J. Biol. Chem., Vol. 275, Issue 50, 39727-39733, December 15, 2000
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From the The transcription factor serum amyloid A
(SAA)-activating factor (SAF), a family of zinc finger proteins,
plays a significant role in the induced expression of the SAA gene.
Activity of SAF is regulated by a phosphorylation event involving
serine/threonine protein kinase (Ray, A., Schatten, H., and Ray,
B. K. (1999) J. Biol. Chem. 274, 4300-4308; Ray,
A., and Ray, B. K. (1998) Mol. Cell. Biol. 18, 7327-7335). However, the identity of the protein kinase has so far
remained unknown. Induction of SAA by phorbol 12-myristate
13-acetate, a known agonist of protein kinase C (PKC), suggested
a potential role of the PKC signaling pathway in the activation
process. The DNA binding activity of endogenous SAF was increased by
agonists of PKC. In vitro phosphorylation of SAF-1 by
PKC-
Activation of Transcription Factor SAF Involves Its
Phosphorylation by Protein Kinase C*
,¶
Department of Veterinary Pathobiology,
University of Missouri, Columbia, Missouri 65211 and the
§ Department of Pharmacology and the Sealy Center for Cancer
Cell Biology, University of Texas Medical Branch,
Galveston, Texas 77555
markedly increased its DNA binding ability. Consistent with
these findings, treatment of cells with activators of PKC or
overexpression of PKC-II in transfected cells increased expression of an SAF-regulated promoter. Further analysis with a GAL4 reporter system indicated that PKC-mediated phosphorylation mostly increases the
DNA binding activity of SAF-1. Together these data indicated that the
PKC signaling pathway plays a major role in controlling expression of
SAF-regulated genes by increasing the interaction between promoter DNA
and phosphorylated SAF.
*
This work was supported by National Institutes of Health
Grant DK49205 (to A. R. and B. K. R.) and CA56869 (to A. P. F.).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.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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