Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics.
Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics.
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DOI：
10.1016/j.gene.2015.06.063
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发表时间：
2015-10-10
期刊：
影响因子：
3.5
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Banerjee U;Cheng X
哺乳动物cAMP直接激活交换蛋白1（Mammalian exchange protein directly activated by cAMP isoform 1，EPAC 1）是由RAPGEF 3基因编码的cAMP感受器的两员家族之一，通过作为Ras样Rap小GTP酶的鸟嘌呤核苷酸交换因子介导cAMP的细胞内功能。广泛的研究表明，EPAC1介导的cAMP信号是高度协调的时空通过形成动态信号体与各种各样的细胞合作伙伴。最近对基因工程小鼠模型的功能分析进一步表明，EPAC 1作为重要的应激反应开关发挥作用，并参与心脏应激、慢性疼痛、癌症和感染性疾病的病理生理条件。这些发现加上EPAC特异性小分子调节剂的开发，验证了EPAC 1作为治疗干预的有希望的靶标。人类基因RAPGEF 3编码EPAC 1蛋白。EPAC是与PKA、CNG和HCN一起沿着的重要的cAMP传感器。已经开发了EPAC 1的选择性调节剂用作药理学探针。EPAC 1信号体的形成允许cAMP信号传导的时空控制。EPAC1与主要的病理生理学状况有关，是一个有吸引力的治疗靶点。
Mammalian exchange protein directly activated by cAMP isoform 1 (EPAC1), encoded by the RAPGEF3 gene, is one of the two-membered family of cAMP sensors that mediate the intracellular functions of cAMP by acting as guanine nucleotide exchange factors for the Ras-like Rap small GTPases. Extensive studies have revealed that EPAC1-mediated cAMP signaling is highly coordinated spatiotemporally through the formation of dynamic signalosomes by interacting with a diverse array of cellular partners. Recent functional analyses of genetically engineered mouse models further suggest that EPAC1 functions as an important stress response switch and is involved in pathophysiological conditions of cardiac stresses, chronic pain, cancer and infectious diseases. These findings, coupled with the development of EPAC specific small molecule modulators, validate EPAC1 as a promising target for therapeutic interventions. Human gene RAPGEF3 encodes for EPAC1 protein. Along with PKA, CNG & HCN, EPAC is an important cAMP sensor. Selective modulators of EPAC1 have been developed for use as pharmacological probes. Formation of EPAC1 signalosomes allows spatiotemporal control of cAMP signaling. EPAC1 is implicated in major pathophysiological conditions and is an attractive therapeutic target.