Sun P, Maurer R A
Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland 97201, USA.
J Biol Chem. 1995 Mar 31;270(13):7041-4. doi: 10.1074/jbc.270.13.7041.
The cAMP response element binding protein (CREB) mediates transcriptional activation in response to the cAMP signaling pathway. Several recent studies have suggested that phosphorylation-dependent interaction of CREB with a co-activator designated CREB binding protein (CBP) is a crucial step in mediating transcriptional responses to cAMP. In the present study we have determined that replacement of Ser142 of CREB with Asp greatly decreases the ability of the cAMP-dependent protein kinase to activate CREB. As Ser142 is located within the region of CREB that interacts with CBP, it seemed quite likely that mutations at this site might interfere with binding to CBP. However, both in vitro and in vivo protein-protein interaction assays revealed that replacement of Ser142 with Asp does not interfere with the binding of CREB to CBP. These studies argue strongly that although the binding of CREB to CBP is necessary, it is not sufficient for transcriptional responses to cAMP.
环磷酸腺苷反应元件结合蛋白（CREB）介导对环磷酸腺苷信号通路的转录激活。最近的几项研究表明，CREB与一种名为环磷酸腺苷反应元件结合蛋白（CBP）的共激活因子之间的磷酸化依赖性相互作用是介导对环磷酸腺苷转录反应的关键步骤。在本研究中，我们确定将CREB的丝氨酸142替换为天冬氨酸会大大降低环磷酸腺苷依赖性蛋白激酶激活CREB的能力。由于丝氨酸142位于CREB与CBP相互作用的区域内，因此该位点的突变很可能会干扰与CBP的结合。然而，体外和体内蛋白质-蛋白质相互作用试验均显示，将丝氨酸142替换为天冬氨酸不会干扰CREB与CBP的结合。这些研究有力地表明，尽管CREB与CBP的结合是必要的，但对于对环磷酸腺苷的转录反应而言并不充分。
