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Title:
Smooth muscle 22α facilitates angiotensin II-induced signaling and vascular contraction | Journal of Molecular Medicine
Description:
Abstract Smooth muscle 22α (SM22α) is involved in stress fiber formation and enhances contractility in vascular smooth muscle cells (VSMCs). In many cases, SM22α acts as an adapter protein to assemble signaling complexes and regulate signaling, but whether SM22α regulates contractile signaling induced by angiotensin II (AngII) remains unclear. To address this issue, we established a hypertension model of Sm22αā/ā mice, and demonstrated that hypertension induced by AngII was attenuated in Sm22αā/ā mice. A decreased vasoconstriction was observed in aortic rings from Sm22αā/ā mice. Furthermore, loss of SM22α resulted in a reduced contractile response to AngII in VSMCs in vitro. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by AngII was impaired following depletion of SM22α, in parallel with a reduced contractility. The decay of ERK1/2 activity was associated with increased expression of mitogen-activated protein kinase phosphatase 3 (MKP3). Inhibition of MKP3 activity rescued ERK1/2 activity. SM22α depletion caused an enhanced interaction of MKP3 with ERK1/2, and a reduced ubiquitination and degradation of MKP3. Knockdown of SM22α extended the half-life of MKP3. In conclusion, SM22α promotes AngII-induced contraction by maintenance of ERK1/2 signaling cascades through facilitating ubiquitination and degradation of MKP3. Key message The vasoconstriction is attenuated in aortic rings from Sm22αā/ā mice. MKP3 mediates dephosphorylation of ERK1/2 in AngII-induced VSMC contraction. SM22α inhibits the interaction of ERK1/2 with MKP3. SM22α promotes ubiquitination and degradation of MKP3. SM22α facilitates AngII-induced contraction by maintenance of ERK1/2 signaling.
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Keywords {š}
article, pubmed, google, scholar, cas, smα, smooth, muscle, vascular, erk, signaling, mkp, kinase, angiotensin, cells, protein, cell, central, contraction, mice, iiinduced, hypertension, biol, privacy, cookies, content, journal, zhang, liu, han, contractile, mol, cancer, dusp, publish, search, facilitates, xie, miao, contractility, induced, angii, reduced, signalregulated, activity, mitogenactivated, phosphatase, degradation, access, chem,
Topics {āļø}
ca2+/calmodulin-dependent kinase ii month download article/chapter ang ii-induced contraction angii-induced vsmc contraction peng chen & mei han 25-kda actin-binding protein reduced contractile response mitogen-activated protein signaling cascades induced molecular medicine aims angiotensin ii full article pdf dual-specific phosphatase-6 erk1/2 signaling cascades dual specificity phosphatases assemble signaling complexes focal adhesion signaling privacy choices/manage cookies agonist-induced regulation related subjects region-specific manner receptor tyrosine kinases thyroid cancer cells mkp3 mediates dephosphorylation atg4b-mediated autophagy lef1 regulates dusp6 vascular contraction mei-ling aj article xie physiol-cell ph 292 physiol-cell ph 299 sm22α promotes ubiquitination regulate signaling article journal erk1/2 signaling european economic area yan-ling lin stress fiber formation cardiovascular system influence neuromast formation sÔnchez-gómez mv valuable technical assistance electronic supplementary material li-li zhao conditions privacy policy ya-juan yin ya-nan shu sustained erk phosphorylation sui-bing miao partial sequence analysis
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headline:Smooth muscle 22α facilitates angiotensin II-induced signaling and vascular contraction
description:Smooth muscle 22α (SM22α) is involved in stress fiber formation and enhances contractility in vascular smooth muscle cells (VSMCs). In many cases, SM22α acts as an adapter protein to assemble signaling complexes and regulate signaling, but whether SM22α regulates contractile signaling induced by angiotensin II (AngII) remains unclear. To address this issue, we established a hypertension model of Sm22αā/ā mice, and demonstrated that hypertension induced by AngII was attenuated in Sm22αā/ā mice. A decreased vasoconstriction was observed in aortic rings from Sm22αā/ā mice. Furthermore, loss of SM22α resulted in a reduced contractile response to AngII in VSMCs in vitro. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by AngII was impaired following depletion of SM22α, in parallel with a reduced contractility. The decay of ERK1/2 activity was associated with increased expression of mitogen-activated protein kinase phosphatase 3 (MKP3). Inhibition of MKP3 activity rescued ERK1/2 activity. SM22α depletion caused an enhanced interaction of MKP3 with ERK1/2, and a reduced ubiquitination and degradation of MKP3. Knockdown of SM22α extended the half-life of MKP3. In conclusion, SM22α promotes AngII-induced contraction by maintenance of ERK1/2 signaling cascades through facilitating ubiquitination and degradation of MKP3.
datePublished:2014-12-17T00:00:00Z
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SM22α
Contractile signaling
MKP3
Vascular smooth muscle cells
Molecular Medicine
Human Genetics
Internal Medicine
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headline:Smooth muscle 22α facilitates angiotensin II-induced signaling and vascular contraction
description:Smooth muscle 22α (SM22α) is involved in stress fiber formation and enhances contractility in vascular smooth muscle cells (VSMCs). In many cases, SM22α acts as an adapter protein to assemble signaling complexes and regulate signaling, but whether SM22α regulates contractile signaling induced by angiotensin II (AngII) remains unclear. To address this issue, we established a hypertension model of Sm22αā/ā mice, and demonstrated that hypertension induced by AngII was attenuated in Sm22αā/ā mice. A decreased vasoconstriction was observed in aortic rings from Sm22αā/ā mice. Furthermore, loss of SM22α resulted in a reduced contractile response to AngII in VSMCs in vitro. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by AngII was impaired following depletion of SM22α, in parallel with a reduced contractility. The decay of ERK1/2 activity was associated with increased expression of mitogen-activated protein kinase phosphatase 3 (MKP3). Inhibition of MKP3 activity rescued ERK1/2 activity. SM22α depletion caused an enhanced interaction of MKP3 with ERK1/2, and a reduced ubiquitination and degradation of MKP3. Knockdown of SM22α extended the half-life of MKP3. In conclusion, SM22α promotes AngII-induced contraction by maintenance of ERK1/2 signaling cascades through facilitating ubiquitination and degradation of MKP3.
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Contractile signaling
MKP3
Vascular smooth muscle cells
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Human Genetics
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email:[email protected]
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name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
name:Key Laboratory of Medical Biotechnology of Hebei Province, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang, Peopleās Republic of China
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