Ca2+/calmodulin-dependent protein kinase IV activates cysteine-rich protein 1 through adjacent CRE and CArG elements

被引:16
作者
Najwer, I
Lilly, B
机构
[1] Med Coll Georgia, Vasc Biol Ctr, Augusta, GA 30912 USA
[2] Med Coll Georgia, Dept Obstet & Gynecol, Augusta, GA 30912 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2005年 / 289卷 / 04期
关键词
smooth muscle; cAMP response element-binding protein; serum response factor;
D O I
10.1152/ajpcell.00098.2005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Ca2+/calmodulin-dependent protein kinase IV activates cysteine-rich protein 1 through adjacent CRE and CArG elements. Am J Physiol Cell Physiol 289: C785-C793, 2005. First published May 25, 2005; doi:10.1152/ajpcell.00098.2005. Smooth muscle-specific transcription is controlled by a multitude of transcriptional regulators that cooperate to drive expression in a temporospatial manner. Previous analysis of the cysteine-rich protein 1 (CRP1/Csrp) gene revealed an intronic enhancer that is sufficient for expression in arterial smooth muscle cells and requires a serum response factor-binding CArG element for activity. The presence of a CArG box in smooth muscle regulatory regions is practically invariant; however, it stands to reason that additional elements contribute to the modulation of transcription in concert with the CArG. Because of the potential importance of other regulatory elements for expression of the CRP1 gene, we sought to identify additional motifs within the enhancer that are necessary for expression. In this effort, we identified a conserved cAMP response element ( CRE) that, when mutated, diminishes the expression of the enhancer in cultured vascular smooth muscle cells. Using transfection and electrophoretic mobility shift assays, we have shown that the CRE binds the cAMP response element-binding protein ( CREB) and is activated by Ca2+/calmodulin-dependent protein kinase IV ( CaMKIV), but not by CaMKII. Furthermore, our data demonstrate that CaMKIV stimulates CRP1 expression not only through the CRE but also through the CArG box. These findings represent evidence of a functional CRE within a smooth muscle-specific gene and provide support for a mechanism in which CREB functions as a smooth muscle determinant through CaMKIV activation.
引用
收藏
页码:C785 / C793
页数:9
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