ArticleAmerican journal of physiology. Heart and circulatory physiology2015
Dual regulation of tumor necrosis factor-α on myosin light chain phosphorylation in vascular smooth muscle.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
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- Psoriasis and Cardiometabolic Diseases: Shared Genetic and Molecular Pathways.International journal of molecular sciences · 2022Review
- Roles of the RhoA-ROCK Signaling Pathway in the Endothelial HACS omega · 2022Article
- S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway.Cell communication and signaling : CCS · 2021Article
- Vascular consequences of inflammation: a position statement from the ESH Working Group on Vascular Structure and Function and the ARTERY Society.Journal of hypertension · 2020Review
- The pathophysiological basis of vascular disease.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Regulates Smooth Muscle Contractility by Modulating CaArteriosclerosis, thrombosis, and vascular biology · 2018Article
- Involvement of inhibitor kappa B kinase 2 (IKK2) in the regulation of vascular tone.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Novel phosphorylated TAK1 species with functional impact on NF-κB and β-catenin signaling in human Cutaneous T-cell lymphoma.Leukemia · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
We previously demonstrated that inhibitor κB kinase 2 (IKK2) is a myosin light chain kinase (MLCK). In the present study, we assess whether the prototypical activator of IKK2 tumor necrosis factor-α (TNF-α) regulates the MLCK activity of IKK2 and thus MLC phosphorylation in vascular smooth muscle cells (VSMCs). Kinase activity assay revealed that TNF-α downregulated the MLCK activity of IKK2 in human VSMCs (HVSMCs). However, Western blot analysis did not demonstrate a significant effect of TNF-α on MLC phosphorylation in HVSMCs, and myograph analysis did not reveal a significant effect of TNF-α on the contraction of the aorta from Sprague-Dawley rats and C57Bl/6j mice, suggesting a dual regulation of MLC phosphorylation by TNF-α. Confirming this notion, TNF-α significantly increased MLC phosphorylation in IKK2(-/-) but not wild-type cells. Furthermore, our results show that TNF-α increased GTP-bound RhoA and MLC phosphatase subunit MYPT1 phosphorylation and markedly reduced MLC phosphorylation in the presence of Rho-kinase inhibitor Y-27632, suggesting that downregulation of MLCK activity of IKK2 by TNF-α is antagonized by simultaneous RhoA/Rho-kinase activation. These results indicate that TNF-α dually regulates MLC phosphorylation through both IKK2 and RhoA/Rho-kinase pathways.
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