A Rac-cGMP signaling pathway
A Rac-cGMP signaling pathway
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DOI：
10.1016/j.cell.2006.11.048
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发表时间：
2007-01-26
期刊：
影响因子：
64.5
通讯作者：
Huang, Xin-Yun
中科院分区：
文献类型：
--
作者：
Guo, Dagang;Tan, Ying-cai;Huang, Xin-Yun
小的GT3-Rac和第二信使cGMP（鸟苷3 '，5'-环一磷酸）是多种细胞功能的关键调节剂。当经由膜信号传导受体被细胞外信号激活时，Rac通过接合下游效应物如p21激活的激酶（PAK）（一种丝氨酸/苏氨酸蛋白激酶）来执行其功能。然而，膜信号受体调节cGMP水平的分子机制尚不清楚。在这里，我们发现了一个信号通路连接Rac细胞cGMP的增加。我们表明，Rac使用PAK直接激活跨膜鸟苷酸环化酶（GC），导致细胞cGMP水平增加。该Rac/PAK/GC/cGMP通路参与血小板衍生生长因子诱导的成纤维细胞迁移和板状伪足形成。我们的研究结果将细胞生理功能的两个重要调节因子联系起来，并为不同受体通过升高细胞cGMP水平来调节生理反应提供了一般机制。
The small GTPase Rac and the second messenger cGMP (guanosine 3',5'-cyclic monophosphate) are critical regulators of diverse cell functions. When activated by extracellular signals via membrane signaling receptors, Rac executes its functions through engaging downstream effectors such as p21-activated kinase (PAK), a serine/threonine protein kinase. However, the molecular mechanism by which membrane signaling receptors regulate cGMP levels is not known. Here we have uncovered a signaling pathway linking Rac to the increase of cellular cGMP. We show that Rac uses PAK to directly activate transmembrane guanylyl cyclases (GCs), leading to increased cellular cGMP levels. This Rac/PAK/GC/cGMP pathway is involved in platelet-derived growth factor-induced fibroblast cell migration and lamellipodium formation. Our findings connect two important regulators of cellular physiological functions and provide a general mechanism for diverse receptors to modulate physiological responses through elevating cellular cGMP levels.