Loriaux M M, Rehfuss R P, Brennan R G, Goodman R H
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9046-50. doi: 10.1073/pnas.90.19.9046.
The ability of basic/leucine zipper transcription factors to form homo- and heterodimers potentially increases the diversity of signaling pathways that can impinge upon a single genetic element. The capacity of these proteins to dimerize in various combinations complicates the analysis of their functional properties, however. To simplify the functional analysis of CREB dimers, we mutated selected residues within the leucine zipper region to generate proteins that could only heterodimerize. These mutants allowed us to determine whether phosphorylation of both CREB subunits was necessary for transcriptional activation. Our results reveal that hemiphosphorylated CREB dimers are half as active as fully phosphorylated dimers. It is possible, therefore, that the degree of phosphorylation of CREB complexes could modulate the transcriptional responses of specific genes to cAMP.
碱性/亮氨酸拉链转录因子形成同二聚体和异二聚体的能力，可能会增加作用于单个遗传元件的信号通路的多样性。然而，这些蛋白质以各种组合形成二聚体的能力，使得对其功能特性的分析变得复杂。为了简化对CREB二聚体的功能分析，我们对亮氨酸拉链区域内的特定残基进行了突变，以生成只能形成异二聚体的蛋白质。这些突变体使我们能够确定两个CREB亚基的磷酸化对于转录激活是否必要。我们的结果表明，半磷酸化的CREB二聚体的活性只有完全磷酸化二聚体的一半。因此，CREB复合物的磷酸化程度有可能调节特定基因对cAMP的转录反应。
