PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2
PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2
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DOI：
10.1074/jbc.274.53.38125
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发表时间：
1999-12-31
影响因子：
4.8
通讯作者：
Bos, JL
中科院分区：
文献类型：
--
作者：
de Rooij, J;Boenink, NM;Bos, JL
小的GTdR Rap 1已经涉及到各种细胞过程，包括细胞形态，增殖和分化的控制。大量细胞表面受体的刺激导致Rap 1的快速激活，即GTP结合形式的增加。这种激活由第二信使如钙、cAMP和甘油二酯介导，但也可能存在其他途径。在这里，我们描述了一个普遍表达的鸟嘌呤核苷酸交换因子200 kDa的激活Rap 1在体内和体外。该交换因子具有两个推定的调节结构域：具有与cAMP结合结构域相关的氨基酸序列的结构域和PDZ结构域。因此，我们将其命名为PDZ-GEF 1。PDZ-GEF与Epac密切相关，Epac是具有真正cAMP结合位点的RAP特异性交换因子，直接受cAMP调节。与cAMP结合结构域相关的结构域，如Epac中的cAMP结合位点，充当负调控结构域。然而，PDZ-GEF 1不与cAMP或cGMP相互作用。有趣的是，PDZ-GEF 1也激活Rap 2，Rap 1的近亲。这是交换因子作用于Rap 2的第一个例子。我们的结论是PDZ-GEF 1是一个鸟嘌呤核苷酸交换因子，具体的Rap 1和Rap 2，这是由负调控结构域控制。
The small GTPase Rap1 has been implicated in a variety of cellular processes including the control of cell morphology, proliferation, and differentiation. Stimulation of a large variety of cell surface receptors results in the rapid activation of Rap1, i.e. an increase in the GTP-bound form. This activation is mediated by second messengers like calcium, cAMP, and diacylglycerol, but additional pathways may exist as well. Here we describe a ubiquitously expressed guanine nucleotide exchange factor of 200 kDa that activates Rap1 both in vivo and in vitro. This exchange factor has two putative regulatory domains: a domain with an amino acid sequence related to cAMP-binding domains and a PDZ domain. Therefore, we named it PDZ-GEF1. PDZ-GEFs are closely related to Epacs, Rap-specific exchange factors with a genuine cAMP binding site, that are directly regulated by cAMP. The domain related to cAMP-binding domains, like the cAMP binding site in Epac, serves as a negative regulatory domain. However, PDZ-GEF1 does not interact with cAMP or cGMP. Interestingly, PDZ-GEF1 also activates Rap2, a close relative of Rap1. This is the first example of an exchange factor acting on Rap2. We conclude that PDZ-GEF1 is a guanine nucleotide exchange factor, specific for Rap1 and Rap2, that is controlled by a negative regulatory domain.