Kawasaki H, Springett G M, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman D E, Graybiel A M
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139, USA.
Science. 1998 Dec 18;282(5397):2275-9. doi: 10.1126/science.282.5397.2275.
cAMP (3',5' cyclic adenosine monophosphate) is a second messenger that in eukaryotic cells induces physiological responses ranging from growth, differentiation, and gene expression to secretion and neurotransmission. Most of these effects have been attributed to the binding of cAMP to cAMP-dependent protein kinase A (PKA). Here, a family of cAMP-binding proteins that are differentially distributed in the mammalian brain and body organs and that exhibit both cAMP-binding and guanine nucleotide exchange factor (GEF) domains is reported. These cAMP-regulated GEFs (cAMP-GEFs) bind cAMP and selectively activate the Ras superfamily guanine nucleotide binding protein Rap1A in a cAMP-dependent but PKA-independent manner. Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling.
环磷酸腺苷（3',5'-环腺苷单磷酸，cAMP）是一种第二信使，在真核细胞中可引发从生长、分化、基因表达至分泌和神经传递等一系列生理反应。这些效应大多归因于cAMP与环磷酸腺苷依赖性蛋白激酶A（PKA）的结合。本文报道了一类cAMP结合蛋白，它们在哺乳动物脑和身体器官中呈差异分布，同时具有cAMP结合结构域和鸟嘌呤核苷酸交换因子（GEF）结构域。这些cAMP调节的GEF（cAMP-GEF）结合cAMP，并以cAMP依赖性但PKA非依赖性的方式选择性激活Ras超家族鸟嘌呤核苷酸结合蛋白Rap1A。我们的研究结果表明，有必要重新阐述cAMP介导的信号传导概念，使其包括与Ras超家族信号传导的直接偶联。
