A family of cAMP-binding proteins that directly activate Rap1
A family of cAMP-binding proteins that directly activate Rap1
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DOI：
10.1126/science.282.5397.2275
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发表时间：
1998-12-18
期刊：
影响因子：
56.9
通讯作者：
Graybiel, AM
中科院分区：
文献类型：
--
作者：
Kawasaki, H;Springett, GM;Graybiel, AM
环腺苷酸（3',5' - 环磷酸腺苷）是一种第二信使，在真核细胞中诱导从生长、分化、基因表达到分泌和神经传递等生理反应。这些效应大多归因于环腺苷酸与环腺苷酸依赖性蛋白激酶A（PKA）的结合。在此，报道了一类在哺乳动物脑和身体器官中差异分布且同时具有环腺苷酸结合结构域和鸟嘌呤核苷酸交换因子（GEF）结构域的环腺苷酸结合蛋白。这些受环腺苷酸调节的鸟嘌呤核苷酸交换因子（环腺苷酸 - 鸟嘌呤核苷酸交换因子）结合环腺苷酸，并以环腺苷酸依赖性但不依赖PKA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，有必要重新构建环腺苷酸介导的信号传导概念，以包括与Ras超家族信号传导的直接偶联。
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.