Gonzalez G A, Yamamoto K K, Fischer W H, Karr D, Menzel P, Biggs W, Vale W W, Montminy M R
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037.
Nature. 1989 Feb 23;337(6209):749-52. doi: 10.1038/337749a0.
Cyclic AMP regulates the expression of a number of genes through a conserved promoter element, the CRE1. Moreover, transcriptional induction by cAMP requires the activation of cAMP-dependent protein kinase (protein kinase A). We have previously characterized the cAMP response element binding protein (CREB) in PC12 cells and brain tissue as a nuclear factor, of relative molecular mass 43,000, whose transcriptional efficacy is regulated by protein kinase A phosphorylation. CREB stimulates transcription on binding to the CRE as a dimer. Experiments suggesting that the dimerization and transcriptional efficacy of CREB are each stimulated by phosphorylation at distinct sites prompted us to suggest that CREB is regulated by multiple kinases in vivo. We now report the isolation of a cDNA clone for rat CREB using amino-acid sequence information from purified CREB protein. Sequence analysis of this CREB cDNA predicts a cluster of protein kinase A, protein kinase C and casein kinase II consensus recognition sites near the N terminus of the protein. The proximity of these potential phosphorylation sites to one another indicates that they may interact either positively or negatively to regulate CREB bioactivity.
环磷酸腺苷（cAMP）通过一个保守的启动子元件CRE1调节多个基因的表达。此外，cAMP介导的转录诱导需要激活cAMP依赖性蛋白激酶（蛋白激酶A）。我们之前已将PC12细胞和脑组织中的cAMP反应元件结合蛋白（CREB）鉴定为一种相对分子质量为43,000的核因子，其转录效力受蛋白激酶A磷酸化作用的调节。CREB作为二聚体与CRE结合时可刺激转录。实验表明，CREB的二聚化和转录效力分别受到不同位点磷酸化的刺激，这促使我们提出CREB在体内受多种激酶调节的观点。我们现在报告利用纯化的CREB蛋白的氨基酸序列信息分离出大鼠CREB的cDNA克隆。对该CREB cDNA的序列分析预测，在该蛋白的N端附近存在一组蛋白激酶A、蛋白激酶C和酪蛋白激酶II的共有识别位点。这些潜在磷酸化位点彼此靠近，表明它们可能通过正向或负向相互作用来调节CREB的生物活性。
