p63RhoGEF：G(q)介导的平滑肌激活的新开关。
p63RhoGEF: a new switch for G(q)-mediated activation of smooth muscle.
机构信息
University of Virginia, Department of Molecular Physiology and Biological Physics, Charlottesville, VA 22908, USA.
出版信息
Trends Cardiovasc Med. 2012 Jul;22(5):122-7. doi: 10.1016/j.tcm.2012.07.007. Epub 2012 Aug 16.
Abstract
In normal and diseased vascular smooth muscle (SM), the RhoA pathway, which is activated by multiple agonists through G protein-coupled receptors (GPCRs), plays a central role in regulating basal tone and peripheral resistance. Multiple RhoA GTP exchange factors (GEFs) are expressed in SM, raising the possibility that specific agonists coupled to specific GPCRs may couple to distinct RhoGEFs and provide novel therapeutic targets. This review focuses on the function and mechanisms of activation of p63RhoGEF (Arhgef 25; GEFT) recently identified in SM and its possible role in selective targeting of RhoA-mediated regulation of basal blood pressure through agonists that couple through G(αq/11).
摘要
在正常和病变的血管平滑肌（SM）中，RhoA 通路通过 G 蛋白偶联受体（GPCRs）被多种激动剂激活，在调节基础张力和外周阻力方面发挥着核心作用。SM 中表达多种 RhoA GTP 交换因子（GEFs），这使得特定的激动剂与特定的 GPCR 偶联可能与不同的 RhoGEFs 偶联，并提供新的治疗靶点。本综述重点介绍了最近在 SM 中鉴定的 p63RhoGEF（Arhgef25；GEFT）的功能和激活机制，以及它在通过与 G（αq/11）偶联的激动剂选择性靶向 RhoA 介导的基础血压调节中的可能作用。
相似文献
1
p63RhoGEF: a new switch for G(q)-mediated activation of smooth muscle.p63RhoGEF：G(q)介导的平滑肌激活的新开关。
Trends Cardiovasc Med. 2012 Jul;22(5):122-7. doi: 10.1016/j.tcm.2012.07.007. Epub 2012 Aug 16.
2
p63RhoGEF couples Gα(q/11)-mediated signaling to Ca2+ sensitization of vascular smooth muscle contractility.p63RhoGEF 将 Gα(q/11)-介导的信号转导与血管平滑肌收缩性的 Ca2+敏化偶联。
Circ Res. 2011 Oct 14;109(9):993-1002. doi: 10.1161/CIRCRESAHA.111.248898. Epub 2011 Sep 1.
3
Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA.白血病相关的Rho鸟嘌呤核苷酸交换因子促进RhoA的Gαq偶联激活。
Mol Cell Biol. 2002 Jun;22(12):4053-61. doi: 10.1128/MCB.22.12.4053-4061.2002.
4
The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA.鸟嘌呤核苷酸交换因子p63RhoGEF，是Gq/11偶联受体信号传导与RhoA之间的特定联系。
J Biol Chem. 2005 Mar 25;280(12):11134-9. doi: 10.1074/jbc.M411322200. Epub 2005 Jan 4.
5
Receptor-dependent RhoA activation in G12/G13-deficient cells: genetic evidence for an involvement of Gq/G11.G12/G13缺陷细胞中依赖受体的RhoA激活：Gq/G11参与的遗传学证据
J Biol Chem. 2003 Aug 1;278(31):28743-9. doi: 10.1074/jbc.M304570200. Epub 2003 May 27.
6
Plasma membrane association of p63 Rho guanine nucleotide exchange factor (p63RhoGEF) is mediated by palmitoylation and is required for basal activity in cells.质膜相关的 p63 Rho 鸟苷酸交换因子（p63RhoGEF）通过棕榈酰化介导，并且是细胞基础活性所必需的。
J Biol Chem. 2011 Sep 30;286(39):34448-56. doi: 10.1074/jbc.M111.273342. Epub 2011 Aug 10.
7
The RhoA-specific guanine nucleotide exchange factor p63RhoGEF binds to activated Galpha(16) and inhibits the canonical phospholipase Cbeta pathway.RhoA特异性鸟嘌呤核苷酸交换因子p63RhoGEF与活化的Gα(16)结合，并抑制经典的磷脂酶Cβ途径。
Cell Signal. 2009 Aug;21(8):1317-25. doi: 10.1016/j.cellsig.2009.03.017. Epub 2009 Apr 5.
8
p63RhoGEF and GEFT are Rho-specific guanine nucleotide exchange factors encoded by the same gene.p63RhoGEF和GEFT是由同一基因编码的Rho特异性鸟嘌呤核苷酸交换因子。
Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):540-6. doi: 10.1007/s00210-004-0926-5. Epub 2004 Apr 7.
9
Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs.Gαq-p63RhoGEF-RhoA复合物的结构揭示了G蛋白偶联受体激活RhoA的一条途径。
Science. 2007 Dec 21;318(5858):1923-7. doi: 10.1126/science.1147554.
10
Kinetics of recruitment and allosteric activation of ARHGEF25 isoforms by the heterotrimeric G-protein Gαq.异三聚体 G 蛋白 Gαq 对 ARHGEF25 异构体的募集和变构激活的动力学。
Sci Rep. 2016 Nov 11;6:36825. doi: 10.1038/srep36825.
引用本文的文献
1
Role of RhoGEFs or RhoGAPs in Pyk2-Mediated RhoA Activation in Depolarization-Induced Contraction of Rat Caudal Arterial Smooth Muscle.Rho鸟苷酸交换因子（RhoGEFs）或Rho鸟苷酸酶激活蛋白（RhoGAPs）在大鼠尾动脉平滑肌去极化诱导收缩中Pyk2介导的RhoA激活中的作用
Int J Mol Sci. 2025 Sep 5;26(17):8676. doi: 10.3390/ijms26178676.
2
New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.帕金森病中RhoA-ROCK信号通路调节因子和抑制剂的新见解
Metab Brain Dis. 2025 Jan 7;40(1):90. doi: 10.1007/s11011-024-01500-x.
3
Bioinformatics analysis of G protein subunit gamma transduction protein 2-autophagy axis in CD11b+ dendritic cells as a potential regulator to skew airway neutrophilic inflammation in asthma endotypes.G 蛋白亚单位γ转导蛋白 2-自噬轴在 CD11b+树突状细胞中的生物信息学分析，作为一种潜在的调节因子，可调节哮喘表型中的气道中性粒细胞炎症。
Immun Inflamm Dis. 2024 Oct;12(10):e70038. doi: 10.1002/iid3.70038.
4
Basal ATP release signals through the P2Y receptor to maintain the differentiated phenotype of vascular smooth muscle cells.基础 ATP 通过 P2Y 受体释放信号，以维持血管平滑肌细胞的分化表型。
Atherosclerosis. 2024 Aug;395:117613. doi: 10.1016/j.atherosclerosis.2024.117613. Epub 2024 May 31.
5
Intracellular signaling pathways of muscarinic acetylcholine receptor-mediated detrusor muscle contractions.毒蕈碱型乙酰胆碱受体介导的逼尿肌收缩的细胞内信号通路。
Am J Physiol Renal Physiol. 2023 Nov 1;325(5):F618-F628. doi: 10.1152/ajprenal.00261.2022. Epub 2023 Sep 7.
6
The role of intracellular calcium and Rho kinase pathways in G protein-coupled receptor-mediated contractions of urinary bladder urothelium and lamina propria.细胞内钙和 Rho 激酶通路在 G 蛋白偶联受体介导的膀胱尿路上皮和固有层收缩中的作用。
Am J Physiol Cell Physiol. 2023 Mar 1;324(3):C787-C797. doi: 10.1152/ajpcell.00441.2022. Epub 2023 Jan 23.
7
GEFT aberrant expression in soft tissue sarcomas.GEFT在软组织肉瘤中的异常表达。
Transl Cancer Res. 2019 Feb;8(1):141-149. doi: 10.21037/tcr.2019.01.16.
8
β2-adrenergic receptor regulates ER-mitochondria contacts.β2-肾上腺素能受体调节内质网-线粒体接触。
Sci Rep. 2021 Nov 2;11(1):21477. doi: 10.1038/s41598-021-00801-w.
9
Regulation of myosin light-chain phosphorylation and its roles in cardiovascular physiology and pathophysiology.肌球蛋白轻链磷酸化的调节及其在心血管生理学和病理生理学中的作用。
Hypertens Res. 2022 Jan;45(1):40-52. doi: 10.1038/s41440-021-00733-y. Epub 2021 Oct 6.
10
RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.RGS 蛋白、GRKs 和β-arrestins 调节哮喘中的 G 蛋白介导的信号通路。
Pharmacol Ther. 2021 Jul;223:107818. doi: 10.1016/j.pharmthera.2021.107818. Epub 2021 Feb 15.
本文引用的文献
1
Does p63RhoGEF, a new key mediator of angiotensin II signalling, play a role in blood pressure regulation and cardiovascular remodelling in humans?血管紧张素II信号传导的新关键介质p63RhoGEF在人类血压调节和心血管重塑中起作用吗？
J Renin Angiotensin Aldosterone Syst. 2011 Dec;12(4):634-6. doi: 10.1177/1470320311407232.
2
Rho protein crosstalk: another social network?Rho 蛋白串扰：另一个社交网络？
Trends Cell Biol. 2011 Dec;21(12):718-26. doi: 10.1016/j.tcb.2011.08.002. Epub 2011 Sep 15.
3
p63RhoGEF couples Gα(q/11)-mediated signaling to Ca2+ sensitization of vascular smooth muscle contractility.p63RhoGEF 将 Gα(q/11)-介导的信号转导与血管平滑肌收缩性的 Ca2+敏化偶联。
Circ Res. 2011 Oct 14;109(9):993-1002. doi: 10.1161/CIRCRESAHA.111.248898. Epub 2011 Sep 1.
4
Plasma membrane association of p63 Rho guanine nucleotide exchange factor (p63RhoGEF) is mediated by palmitoylation and is required for basal activity in cells.质膜相关的 p63 Rho 鸟苷酸交换因子（p63RhoGEF）通过棕榈酰化介导，并且是细胞基础活性所必需的。
J Biol Chem. 2011 Sep 30;286(39):34448-56. doi: 10.1074/jbc.M111.273342. Epub 2011 Aug 10.
5
Real-time visualization of heterotrimeric G protein Gq activation in living cells.活细胞中三聚体 G 蛋白 Gq 激活的实时可视化。
BMC Biol. 2011 May 27;9:32. doi: 10.1186/1741-7007-9-32.
6
Role of rho kinase in the functional and dysfunctional tonic smooth muscles.Rho 激酶在功能和非功能紧张性平滑肌中的作用。
Trends Pharmacol Sci. 2011 Jul;32(7):384-93. doi: 10.1016/j.tips.2011.03.005. Epub 2011 Apr 15.
7
Cell signaling of angiotensin II on vascular tone: novel mechanisms.血管紧张素 II 对血管张力的细胞信号转导：新机制。
Curr Hypertens Rep. 2011 Apr;13(2):122-8. doi: 10.1007/s11906-011-0187-x.
8
The role of Rho protein signaling in hypertension.Rho 蛋白信号通路在高血压中的作用。
Nat Rev Cardiol. 2010 Nov;7(11):637-47. doi: 10.1038/nrcardio.2010.136. Epub 2010 Aug 31.
9
p63RhoGEF--a key mediator of angiotensin II-dependent signaling and processes in vascular smooth muscle cells.p63RhoGEF——血管平滑肌细胞中血管紧张素 II 依赖性信号转导和过程的关键介质。
FASEB J. 2010 Dec;24(12):4865-76. doi: 10.1096/fj.10-155499. Epub 2010 Aug 25.
10
Galpha16 interacts with Class IA phosphatidylinositol 3-kinases and inhibits Akt signaling.Galpha16 与 IA 类磷酸肌醇 3-激酶相互作用并抑制 Akt 信号转导。
Cell Signal. 2010 Sep;22(9):1379-87. doi: 10.1016/j.cellsig.2010.05.008. Epub 2010 May 12.
Zotero 插件