Promoter-binding activity of inflammation-responsive transcription factor SAF is regulated by cyclic AMP signaling pathway.
Promoter-binding activity of inflammation-responsive transcription factor SAF is regulated by cyclic AMP signaling pathway.
复制标题
炎症反应转录因子 SAF 的启动子结合活性受环 AMP 信号通路调节。
DOI:
10.1089/10445490252810294
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发表时间:
2002
期刊:
影响因子:
--
通讯作者:
Ray,BimalK
中科院分区:
文献类型:
--
作者:
Ray,Alpana;Kumar,Deepak;Ray,BimalK
The serum amyloid A activating factor (SAF) was identified as a family of inducible transcription factors that is activated by many mediators of inflammation. Its activation involves a phosphorylation event, whose mechanism is not fully understood. Here, we show that cAMP treatment of several cell types, including mouse liver-derived BNL CL.2, human monocyte-derived THP-1, and a primary culture of vascular smooth muscle cells from porcine aorta, activated cellular SAF's ability to bind DNA. The protein kinase A (PKA) activity in cytoplasmic extracts of cAMP-treated cells was responsible for the potentiation of the DNA-binding activity of the cellular SAF proteins. Furthermore, treatment of nuclear extracts of untreated cells with purified PKA increased the DNA-binding activity of cellular SAF proteins, and specific inhibitors of PKA abrogated the enhanced DNA-binding ability of SAF in the cAMP-treated cells. Consistent with these findings, overexpression of the catalytic subunit of PKA markedly increased expression of the SAF-regulated promoter. These results imply a functional role for the previously detected protein-protein interaction between SAF-1 transcription factor and the catalytic subunit of PKA and further demonstrate the consequences of cAMP-mediated signaling for the expression of SAF-regulated genes.