ArticleMolecular biology of the cell2010
Abl tyrosine kinase phosphorylates nonmuscle Myosin light chain kinase to regulate endothelial barrier function.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 106 citations in OpenAlex.
- Article
- Loss of myosin light chain kinase induces the cellular senescence associated secretory phenotype to promote breast epithelial cell migration.Scientific reports · 2024Article
- Genetic and epigenetic regulation of cortactin (CTTN) by inflammatory factors and mechanical stress in human lung endothelial cells.Bioscience reports · 2024Article
- A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.Annual review of physiology · 2024Review
- New Regulatory roles for Human Serum Amyloid A.International journal of research in oncology · 2024Article
- Circadian disruption dysregulates lung gene expression associated with inflammatory lung injury.Frontiers in immunology · 2024Article
- Lamellipodia dynamics and microrheology in endothelial cell paracellular gap closure.Biophysical journal · 2023Article
- Enabled primarily controls filopodial morphology, not actin organization, in the TSM1 growth cone inMolecular biology of the cell · 2023Article
- A new view of axon growth and guidance grounded in the stochastic dynamics of actin networks.Open biology · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- An Actin-, Cortactin- and Ena-VASP-Linked Complex Contributes to Endothelial Cell Focal Adhesion and Vascular Barrier Regulation.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- A cortactin CTTN coding SNP contributes to lung vascular permeability and inflammatory disease severity in African descent subjects.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Hemin-Induced Endothelial Dysfunction and Endothelial to Mesenchymal Transition in the Pathogenesis of Pulmonary Hypertension Due to Chronic Hemolysis.International journal of molecular sciences · 2022Article
- Cortactin in Lung Cell Function and Disease.International journal of molecular sciences · 2022Review
- Critical role for the lung endothelial nonmuscle myosin light-chain kinase isoform in the severity of inflammatory murine lung injury.Pulmonary circulation · 2022Article
- Barrier maintenance by S1P during inflammation and sepsis.Tissue barriers · 2021Review
- Postnatal development alters functional compartmentalization of myosin light chain kinase in ovine carotid arteries.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Depletion of Arg/Abl2 improves endothelial cell adhesion and prevents vascular leak during inflammation.Angiogenesis · 2021Article
- Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability.Frontiers in physiology · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Nonmuscle myosin light chain kinase (nmMLCK), a multi-functional cytoskeletal protein critical to vascular homeostasis, is highly regulated by tyrosine phosphorylation. We identified multiple novel c-Abl-mediated nmMLCK phosphorylation sites by mass spectroscopy analysis (including Y231, Y464, Y556, Y846) and examined their influence on nmMLCK function and human lung endothelial cell (EC) barrier regulation. Tyrosine phosphorylation of nmMLCK increased kinase activity, reversed nmMLCK-mediated inhibition of Arp2/3-mediated actin polymerization, and enhanced binding to the critical actin-binding phosphotyrosine protein, cortactin. EC challenge with sphingosine 1-phosphate (S1P), a potent barrier-enhancing agonist, resulted in c-Abl and phosphorylated nmMLCK recruitment into caveolin-enriched microdomains, rapid increases in Abl kinase activity, and spatial targeting of c-Abl to barrier-promoting cortical actin structures. Conversely, reduced c-Abl expression in EC (siRNA) markedly attenuated S1P-mediated cortical actin formation, reduced the EC modulus of elasticity (assessed by atomic force microscopy), reduced nmMLCK and cortactin tyrosine phosphorylation, and attenuated S1P-mediated barrier enhancement. These studies indicate an essential role for Abl kinase in vascular barrier regulation via posttranslational modification of nmMLCK and strongly support c-Abl-cortactin-nmMLCK interaction as a novel determinant of cortical actin-based cytoskeletal rearrangement critical to S1P-mediated EC barrier enhancement.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.