CYCLIC-AMP STIMULATES SOMATOSTATIN GENE-TRANSCRIPTION BY PHOSPHORYLATION OF CREB AT SERINE-133
CYCLIC-AMP STIMULATES SOMATOSTATIN GENE-TRANSCRIPTION BY PHOSPHORYLATION OF CREB AT SERINE-133
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DOI：
10.1016/0092-8674(89)90013-5
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发表时间：
1989-11-17
期刊：
影响因子：
64.5
通讯作者：
MONTMINY, MR
中科院分区：
文献类型：
--
作者：
GONZALEZ, GA;MONTMINY, MR
在这篇论文中，我们证明了在体内用forskolin处理PC12细胞后，CREB Ser-133位点的磷酸化被诱导了6倍。相比之下，在激酶a缺陷的PC12细胞系A126- 1b2 （A126）中没有观察到这种诱导。使用对cAMP无反应的F9畸胎癌细胞，我们启动了一系列瞬时表达实验，以建立CREB磷酸化与cAMP反应基因反式激活之间的因果关系。通过体外诱变克隆的CREB cDNA Ser-133处的激酶A磷酸化位点灭活，完全消除了CREB的转录活性。由于含有酸性残基代替Ser-133磷受体的CREB突变体也具有转录失活，这些结果表明，CREB的磷酸化可能通过一种机制刺激转录，而不仅仅是提供负电荷。
In this paper, we demonstrate that phosphorylation of CREB at Ser-133 is induced 6-fold in vivo, following treatment of PC12 cells with forskolin. By contrast, no such induction was observed in the kinase A-deficient PC12 line A126-1B2 (A126). Using F9 teratocarcinoma cells, which are unresponsive to cAMP, we initiated a series of transient expression experiments to establish a causal link between phosphorylation of CREB and trans-activation of cAMP-responsive genes. Inactivating the kinase A phosphorylation site by in vitro mutagenesis of the cloned CREB cDNA at Ser-133 completely abolished CREB transcription activity. As CREB mutants containing acidic residues in place of the Ser-133 phosphoacceptor were also transcriptionally inactive, these results suggest that phosphorylation of CREB may stimulate transcription by a mechanism other than by simply providing negative charge.