Analysis of disease susceptibility genes on Rho family signaling molecules

Rho家族小GTP酶调节细胞粘附和细胞运动。其中，Rho参与平滑肌收缩和细胞迁移的调节。已有研究表明Rho/Rho激酶的异常激活通过促进细胞收缩和迁移与血管痉挛、高血压和动脉粥样硬化的进展相关。然而，其他Rho家族GTP酶如Rac和Cdc 42的参与较少被记录，尽管Rac和Cdc 42通常被认为在细胞迁移和粘附中是重要的，并且与Rho信号通路交叉。内皮型一氧化氮合酶（eNOS）产生一氧化氮（NO），参与心血管系统的多种生理功能。eNOS通过Ser 1177的磷酸化和Thr 495的去磷酸化激活。然而，很少有人知道的蛋白激酶负责在Thr 495磷酸化。在这项研究中，vie发现Rho激酶在体外和内皮细胞中都在Thr 495磷酸化eNOS， ...更多信息 提示Rbo-激酶可通过直接磷酸化eNOS抑制内皮中NO的产生。PAR-3、PAR-6和aPAC的极性复合物在各种细胞极化事件中起作用，PAR-3与RacGEF、STEP相互作用，导致Rac激活。Rho和Rbo激酶在某些细胞类型中拮抗Rae，但其潜在机制仍然难以捉摸。我们发现Rho激酶磷酸化PAR-3的Thr 333位，从而破坏了PAR-3与aPAC和PAR-6的相互作用，Rlxykinam也磷酸化STEF并调节其功能。我们认为RholRbo激酶通过PAR-3和STEF的磷酸化抑制Rae活性。以往的研究表明Rbo家族的GTP酶与心血管疾病有关。本研究假设Rho家族信号分子中存在心血管疾病的易感基因。我们分析了Rho家族信号分子的38个gems（57个SNP）与冠状动脉痉挛的关联，并发现ARHGAP 9（Ala 370 Ser）与冠状动脉痉挛显著相关，ARHGAP 9是体内Rac的负调控因子。少

Rho family small GTPases regulate cell adhesion and cell motility. Among them, Rho participates in the regulation of smooth muscle contraction and cell migration. It has been suggested that the aberrant activation of Rho/Rho-kinase is associated with vasospasm, hypertension and progression of atherosclerosis via promotion of cell contraction and migration. However, involvement of other Rho .family GTPases such as Rac and Cdc42 has been less documented, even though Rac and Cdc42 are generally believed to be important in cell migration and adhesion and to cross talk with Rho signaling pathway.1. Endothelial NOS (eNOS) produces NO, which is involved in various physiological functions of the cardiovascular system. eNOS is activated by phosphorylation at Ser1177, and by dephosphorylaton at Thr495. However, little is known about the protein kinases responsible for phosphorylation at Thr495. In this study, vie found that Rho-kinase phosphorylated eNOS at Thr495 both in vitro and endothelium, … More suggesting that Rbo-kinase can suppress NO production in endothelium through direct phosphorylation of eNOS.2. A polarity complex of PAR-3, PAR-6, and aPAC functions in various cell polarization events, and PAR-3 interacts with RacGEF, STEP which leads to Rac activation. Rho and Rbo-kinase antagonize Rae in certain cell types, but the underlying mechanisms remain elusive. We here hind that Rho-kinase phospborylated PAR-3 at Thr333 and thereby disrupted its interaction with aPAC and PAR-6, and that Rlxykinam also phosphorylated STEF and modulated its functions. We propose that RholRbo-Kinase inhibits Rae activity through phosphorylation of PAR-3 and STEF.3. Previous reports have shown that Rbo family GTPases are related to cardiovascular diseases. In this study, we hypothesized that there exist susceptibility genes f cardiovascular diseases in Rho family signaling molecules. We analyzed association of 38 gems (57 SNPs) of Rho family signaling molecules with coronary artery spasm, and found significant association of ARHGAP9 (Ala370Ser), which is negative regulator for Rac in vivo. Less