Endothelial Scaffolding Protein ENH (Enigma Homolog Protein) Promotes PHLPP2 (Pleckstrin Homology Domain and Leucine-Rich Repeat Protein Phosphatase 2)-Mediated Dephosphorylation of AKT1 and eNOS (Endothelial NO Synthase) Promoting Vascular Remodeling.
Abstract | OBJECTIVE: CONCLUSIONS: ENH forms a complex with AKT1 and its phosphatase PHLPP2 to negatively regulate AKT1 activation in the artery endothelium. AKT1 deactivation, a decrease in nitric oxide generation, and subsequent neointima formation induced by vascular injury are mediated by ENH and PHLPP2. ENH and PHLPP2 are thus new proatherosclerotic factors that could be therapeutically targeted.
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Authors | Jiaqi Huang, Changhong Cai, Tianyu Zheng, Xinyan Wu, Dongfei Wang, Kaijie Zhang, Bocheng Xu, Ruochen Yan, Hui Gong, Jie Zhang, Yueli Shi, Zhiyong Xu, Xue Zhang, Xuemin Zhang, Tao Shang, Jianhong Zhou, Xiaogang Guo, Chunlai Zeng, En Yin Lai, Changchun Xiao, Ju Chen, Shu Wan, Wen-Hsien Liu, Yuehai Ke, Hongqiang Cheng |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 40
Issue 7
Pg. 1705-1721
(07 2020)
ISSN: 1524-4636 [Electronic] United States |
PMID | 32268790
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- ENH protein, mouse
- LIM Domain Proteins
- Microfilament Proteins
- PDLIM5 protein, human
- Nitric Oxide
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
- Akt1 protein, mouse
- Proto-Oncogene Proteins c-akt
- PHLPP2 protein, human
- PHLPP2 protein, mouse
- Phosphoprotein Phosphatases
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Topics |
- Adaptor Proteins, Signal Transducing
(deficiency, genetics, metabolism)
- Animals
- Atherosclerosis
(enzymology, pathology, physiopathology)
- Carotid Artery Injuries
(enzymology, genetics, pathology, physiopathology)
- Carotid Artery, Common
(enzymology, pathology, physiopathology)
- Cells, Cultured
- Coronary Artery Disease
(enzymology, pathology, physiopathology)
- Disease Models, Animal
- Human Umbilical Vein Endothelial Cells
(enzymology)
- Humans
- LIM Domain Proteins
(genetics, metabolism)
- Mice, Inbred C57BL
- Mice, Knockout
- Microfilament Proteins
(deficiency, genetics, metabolism)
- Neointima
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Phosphoprotein Phosphatases
(deficiency, genetics, metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Signal Transduction
- Vascular Remodeling
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