The Rac-cGMP Signaling Pathway

Rac-cGMP 信号通路

• 批准号: 8208116
• 负责人: Xin-Yun Huang
• 金额: $ 33.96万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208116
• 关键词: Actins; Allosteric Regulation; Biochemical; Blood Vessels; Cardiovascular Diseases; Cardiovascular Physiology; Catalytic Domain; Cyclic GMP; Cytoskeletal Modeling; Development; Guanosine Triphosphate Phosphohydrolases; Guanylate Cyclase; Health; Human; In Vitro; Investigation; Link; Mediating; Membrane; Molecular; Monomeric GTP-Binding Proteins; Pathway interactions; Phosphotransferases; Physiological; Physiological Processes; Platelet-Derived Growth Factor; Protein Kinase; Receptor Signaling; Reporting; Research; Second Messenger Systems; Signal Pathway; Signal Transduction; Signaling Molecule; System; Vascular Endothelial Growth Factors; Vascular Permeabilities; atrial natriuretic factor receptor A; cell motility; in vivo; mouse model; novel; p21 activated kinase; public health relevance; receptor; response; second messenger

Project Description The long-term objective of this project is to understand the signaling mechanisms and physiological functions of the newly discovered Rac-cGMP pathway. Many membrane-signaling receptors can increase the cellular levels of the ubiquitous second messenger cyclic GMP (cGMP). However, the molecular mechanism by which these membrane-signaling receptors increased cGMP was not known. We recently uncovered a new Rac-cGMP signaling pathway. The small G protein Rac uses its effector PAK (p21-activated kinase) to allosterically activate transmembrane guanylyl cyclases (GCs). These findings reveal a general mechanism for diverse signaling receptors to modulate physiological responses through cGMP. Although the kinase activity of PAK is required, PAK does not directly phosphorylate GCs. Instead, autophosphorylation of PAK is needed to maintain its activated configuration. The active form of PAK then allosterically activates transmembrane GCs. The main focus of this application is on the biochemical mechanism by which Rac, through its effector PAK, regulates the activity of transmembrane guanylyl cyclases. We will investigate the allosteric activation of transmembrane guanylyl cyclases by PAK in the Specific Aim 1. In the Specific Aim 2, we will explore the signaling molecules downstream of cGMP. We will investigate the physiological function of the Rac-cGMP pathway in the Specific Aim 3.

项目描述

项目成果

A new Rac/PAK/GC/cGMP signaling pathway.

• DOI: 10.1007/s11010-009-0327-7
• 发表时间: 2010-01
• 期刊: MOLECULAR AND CELLULAR BIOCHEMISTRY
• 影响因子: 4.3
• 作者: Guo, Dagang;Zhang, J. Jillian;Huang, Xin-Yun
• 通讯作者: Huang, Xin-Yun

Stat3 is essential for neuronal differentiation through direct transcriptional regulation of the Sox6 gene.

• DOI: 10.1016/j.febslet.2010.11.030
• 发表时间: 2011-01-03
• 期刊: FEBS letters
• 影响因子: 3.5
• 作者: Snyder M;Huang XY;Zhang JJ
• 通讯作者: Zhang JJ