{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:47:07Z","timestamp":1790668027438,"version":"4.1.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL120954"],"award-info":[{"award-number":["HL120954"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL096640"],"award-info":[{"award-number":["HL096640"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["GM109095"],"award-info":[{"award-number":["GM109095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA 17SDG33660381"],"award-info":[{"award-number":["AHA 17SDG33660381"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0231739","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T18:07:55Z","timestamp":1588270075000},"page":"e0231739","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Focal adhesion kinase and Src mediate microvascular hyperpermeability caused by fibrinogen- \u03b3C- terminal fragments"],"prefix":"10.1371","volume":"15","author":[{"given":"Xiaohua","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-206X","authenticated-orcid":true,"given":"Rebecca A.","family":"Eitnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-3014","authenticated-orcid":true,"given":"Richard S.","family":"Beard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-676X","authenticated-orcid":true,"given":"Jamie E.","family":"Meegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Aponte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-2962","authenticated-orcid":true,"given":"Peter R.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mack H.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"issue":"1","key":"pone.0231739.ref001","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"JC Chapin","year":"2015","journal-title":"Blood reviews"},{"key":"pone.0231739.ref002","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1053\/euhj.1998.1454","article-title":"Fibrin monomer antigen: a novel marker of mortality in acute myocardial infarction","volume":"20","author":"F Kontny","year":"1999","journal-title":"European Heart Journal"},{"issue":";9","key":"pone.0231739.ref003","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1136\/jnnp.2010.230870","article-title":"Usefulness of measurement of fibrinogen, D-dimer, D-dimer\/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke","volume":"82","author":"FJ Alvarez-Perez","year":"2011","journal-title":"Journal of Neurology, Neurosurgery & Psychiatry"},{"issue":"6","key":"pone.0231739.ref004","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00109-006-0051-7","article-title":"Fibrin(ogen) and its fragments in the pathophysiology and treatment of myocardial infarction","volume":"84","author":"K Zacharowski","year":"2006","journal-title":"Journal of Molecular Medicine"},{"issue":"3","key":"pone.0231739.ref005","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1161\/ATVBAHA.108.180950","article-title":"Fibrinogen-gamma C-terminal fragments induce endothelial barrier dysfunction and microvascular leak via integrin-mediated and RhoA-dependent mechanism","volume":"29","author":"M Guo","year":"2009","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"pone.0231739.ref006","article-title":"Regulation of Endothelial Barrier Function","author":"SY Yuan","year":"2010","journal-title":"Integrated Systems Physiology: From Molecule to Function to Disease"},{"issue":"1","key":"pone.0231739.ref007","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1152\/physrev.00012.2005","article-title":"Signaling Mechanisms Regulating Endothelial Permeability","volume":"86","author":"D Mehta","year":"2006","journal-title":"Physiological Reviews"},{"issue":"1","key":"pone.0231739.ref008","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.devcel.2011.11.002","article-title":"VEGF-induced vascular permeability is mediated by FAK","volume":"22","author":"XL Chen","year":"2012","journal-title":"Developmental Cell"},{"key":"pone.0231739.ref009","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1017\/S1462399409001112","article-title":"Molecular mechanisms of endothelial hyperpermeability: implications in inflammation","volume":"11","author":"P Kumar","year":"2009","journal-title":"Expert reviews in molecular medicine"},{"issue":"Pt 2","key":"pone.0231739.ref010","first-page":"359","article-title":"Endothelial focal adhesions and barrier function","volume":"569","author":"MH Wu","year":"2005","journal-title":"The Journal of Physiology"},{"issue":"4","key":"pone.0231739.ref011","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1537-1891(03)00010-7","article-title":"Protein kinase signaling in the modulation of microvascular permeability","volume":"39","author":"SY Yuan","year":"2002","journal-title":"Vascular Pharmacology"},{"issue":"1","key":"pone.0231739.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-4889(01)00123-9","article-title":"Biochemical signals and biological responses elicited by the focal adhesion kinase","volume":"1540","author":"MD Schaller","year":"2001","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Molecular Cell Research"},{"issue":"2","key":"pone.0231739.ref013","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/10739680590905251","article-title":"Focal Adhesion Kinase in Neutrophil\u2010Induced Microvascular Hyperpermeability","volume":"12","author":"M Guo","year":"2005","journal-title":"Microcirculation"},{"issue":"Pt 3","key":"pone.0231739.ref014","first-page":"691","article-title":"Focal adhesion kinase mediates porcine venular hyperpermeability elicited by vascular endothelial growth factor","volume":"552","author":"MH Wu","year":"2003","journal-title":"The Journal of Physiology"},{"issue":"3","key":"pone.0231739.ref015","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/path.4911","article-title":"Focal Adhesion Kinase (FAK) tyrosine 397E mutation restores the vascular leakage defect in endothelium\u2010specific FAK\u2010kinase dead mice","volume":"242","author":"AN Alexopoulou","year":"2017","journal-title":"The Journal of Pathology"},{"key":"pone.0231739.ref016","doi-asserted-by":"crossref","first-page":"14090","DOI":"10.1038\/srep14090","article-title":"Role of Src in Vascular Hyperpermeability Induced by Advanced Glycation End Products","volume":"5","author":"W Zhang","year":"2015","journal-title":"Scientific Reports"},{"issue":"5","key":"pone.0231739.ref017","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.ceb.2006.08.011","article-title":"Integrin-regulated FAK-Src signaling in normal and cancer cells","volume":"18","author":"SK Mitra","year":"2006","journal-title":"Curr Opin Cell Biol"},{"issue":"3","key":"pone.0231739.ref018","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1128\/MCB.14.3.1680","article-title":"Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src","volume":"14","author":"MD Schaller","year":"1994","journal-title":"Mol Cell Biol"},{"issue":"6","key":"pone.0231739.ref019","doi-asserted-by":"crossref","first-page":"L1232","DOI":"10.1152\/ajplung.00109.2006","article-title":"TNF-\u03b1 increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia","volume":"291","author":"DJ Angelini","year":"2006","journal-title":"American Journal of Physiology-Lung Cellular and Molecular Physiology"},{"issue":"6","key":"pone.0231739.ref020","doi-asserted-by":"crossref","first-page":"C1745","DOI":"10.1152\/ajpcell.00230.2002","article-title":"Src-dependent, neutrophil-mediated vascular hyperpermeability and \u03b2-catenin modification","volume":"283","author":"JH Tinsley","year":"2002","journal-title":"American Journal of Physiology-Cell Physiology"},{"issue":"4","key":"pone.0231739.ref021","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1074\/jbc.M511248200","article-title":"Suppression of RhoA Activity by Focal Adhesion Kinase-induced Activation of p190RhoGAP: ROLE IN REGULATION OF ENDOTHELIAL PERMEABILITY","volume":"281","author":"M Holinstat","year":"2006","journal-title":"Journal of Biological Chemistry"},{"issue":"4","key":"pone.0231739.ref022","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1128\/MCB.00841-10","article-title":"Phosphorylation of Trask by Src Kinases Inhibits Integrin Clustering and Functions in Exclusion with Focal Adhesion Signaling","volume":"31","author":"DS Spassov","year":"2011","journal-title":"Molecular and Cellular Biology"},{"issue":"8","key":"pone.0231739.ref023","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1242\/jcs.098087","article-title":"Actin stress fibers\u2013assembly, dynamics and biological roles","volume":"125","author":"S Tojkander","year":"2012","journal-title":"Journal of Cell Science"},{"issue":"11","key":"pone.0231739.ref024","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1161\/01.RES.0000020402.73609.F1","article-title":"Myosin Light Chain Phosphorylation in Neutrophil-Stimulated Coronary Microvascular Leakage","volume":"90","author":"SY Yuan","year":"2002","journal-title":"Circulation Research"},{"issue":"3","key":"pone.0231739.ref025","doi-asserted-by":"crossref","first-page":"H1057","DOI":"10.1152\/ajpheart.00841.2003","article-title":"Involvement of RhoA and Rho kinase in neutrophil-stimulated endothelial hyperpermeability","volume":"286","author":"JW Breslin","year":"2003","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"2","key":"pone.0231739.ref026","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cbi.2007.08.006","article-title":"Regulation of endothelial permeability by Src kinase signaling: vascular leakage versus transcellular transport of drugs and macromolecules","volume":"171","author":"G Hu","year":"2008","journal-title":"Chem Biol Interact"},{"issue":"7","key":"pone.0231739.ref027","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1161\/CIRCRESAHA.109.201673","article-title":"Phosphorylation of caveolin-1 regulates oxidant-induced pulmonary vascular permeability via paracellular and transcellular pathways","volume":"105","author":"Y Sun","year":"2009","journal-title":"Circ Res"},{"issue":"4","key":"pone.0231739.ref028","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/01.shk.0000079425.0000.db","article-title":"Myosin light chain kinase-dependent microvascular hyperpermeability in thermal injury","volume":"20","author":"Q Huang","year":"2003","journal-title":"Shock"},{"issue":"6","key":"pone.0231739.ref029","doi-asserted-by":"crossref","first-page":"L1218","DOI":"10.1152\/ajplung.2000.279.6.L1218","article-title":"Reversibility of increased microvessel permeability in response to VE-cadherin disassembly","volume":"279","author":"X Gao","year":"2000","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"pone.0231739.ref030","doi-asserted-by":"crossref","first-page":"12823","DOI":"10.1038\/ncomms12823","article-title":"Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in systematic inflammatory response syndrome","volume":"7","author":"RS Beard","year":"2016","journal-title":"Nature Communications"},{"issue":"4","key":"pone.0231739.ref031","doi-asserted-by":"crossref","first-page":"C977","DOI":"10.1152\/ajpcell.90607.2007","article-title":"VE-cadherin and \u03b2-catenin binding dynamics during histamine-induced endothelial hyperpermeability","volume":"294","author":"M Guo","year":"2008","journal-title":"American journal of physiology Cell physiology"},{"key":"pone.0231739.ref032","article-title":"AKT2 maintains brain endothelial claudin-5 expression and selective activation of IR\/AKT2\/FOXO1-signaling reverses barrier dysfunction","author":"RS Beard","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"issue":"7","key":"pone.0231739.ref033","first-page":"2430","article-title":"Src family kinase inhibitor PP2 restores the E-cadherin\/catenin cell adhesion system in human cancer cells and reduces cancer metastasis","volume":"8","author":"JS Nam","year":"2002","journal-title":"Clin Cancer Res"},{"key":"pone.0231739.ref034","doi-asserted-by":"crossref","first-page":"18476","DOI":"10.1038\/srep18476","article-title":"Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration","volume":"5","author":"J-C Wu","year":"2015","journal-title":"Scientific Reports"},{"key":"pone.0231739.ref035","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.mvr.2015.03.007","article-title":"JUNCTIONAL COMPLEX AND FOCAL ADHESION REARRANGEMENT MEDIATES PULMONARY ENDOTHELIAL BARRIER ENHANCEMENT BY FTY720 S-PHOSPHONATE","volume":"99","author":"L Wang","year":"2015","journal-title":"Microvascular research"},{"issue":"1","key":"pone.0231739.ref036","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev-physiol-021909-135833","article-title":"Regulation of Endothelial Permeability via Paracellular and Transcellular Transport Pathways","volume":"72","author":"Y Komarova","year":"2010","journal-title":"Annual Review of Physiology"},{"issue":"3","key":"pone.0231739.ref037","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/cvr\/cvt075","article-title":"Localized RhoA GTPase activity regulates dynamics of endothelial monolayer integrity","volume":"99","author":"R Szulcek","year":"2013","journal-title":"Cardiovascular Research"},{"issue":"12","key":"pone.0231739.ref038","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0960-9822(00)00537-6","article-title":"Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism","volume":"10","author":"WT Arthur","year":"2000","journal-title":"Curr Biol"},{"issue":"2","key":"pone.0231739.ref039","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1083\/jcb.201307067","article-title":"Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function","volume":"204","author":"C Jean","year":"2014","journal-title":"J Cell Biol"},{"issue":"5","key":"pone.0231739.ref040","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1097\/TA.0b013e31828cc967","article-title":"Usefulness of fibrin degradation products and d-dimer levels as biomarkers that reflect the severity of trauma","volume":"74","author":"S Hagiwara","year":"2013","journal-title":"J Trauma Acute Care Surg"},{"issue":"9","key":"pone.0231739.ref041","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nrc3792","article-title":"FAK in cancer: mechanistic findings and clinical applications","volume":"14","author":"FJ Sulzmaier","year":"2014","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"pone.0231739.ref042","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1074\/jbc.273.1.577","article-title":"SH2- and SH3-mediated Interactions between Focal Adhesion Kinase and Src","volume":"273","author":"JW Thomas","year":"1998","journal-title":"Journal of Biological Chemistry"},{"issue":"8","key":"pone.0231739.ref043","doi-asserted-by":"crossref","first-page":"761","DOI":"10.4161\/cbt.25185","article-title":"Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy","volume":"14","author":"M Heffler","year":"2013","journal-title":"Cancer Biology & Therapy"},{"issue":"20","key":"pone.0231739.ref044","doi-asserted-by":"crossref","first-page":"17199","DOI":"10.1074\/jbc.M011185200","article-title":"The Role of the Src Homology 3-Src Homology 2 Interface in the Regulation of Src Kinases","volume":"276","author":"ST Arold","year":"2001","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"pone.0231739.ref045","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/CIRCULATIONAHA.110.988915","article-title":"nmMLCK deficiency ameliorates atherosclerosis in ApoE-deficient mice via reduced endothelial barrier dysfunction and monocyte migration","volume":"124","author":"C Sun","year":"2011","journal-title":"Circulation"},{"key":"pone.0231739.ref046","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev.cellbio.13.1.513","article-title":"Cellular functions regulated by Src family kinases","volume":"13","author":"SM Thomas","year":"1997","journal-title":"Annu. Rev. Cell Dev. Biol"},{"key":"pone.0231739.ref047","doi-asserted-by":"crossref","first-page":"6538","DOI":"10.1073\/pnas.86.17.6538","article-title":"Selective expression of a protein-tyrosine kinase, p56lyn, in hematopoietic cells and association with production of human T-cell lymphotropic virus type I","volume":"86","author":"Y Yamanashi","year":"1989","journal-title":"PNAS"},{"issue":"36","key":"pone.0231739.ref048","doi-asserted-by":"crossref","first-page":"31906","DOI":"10.1074\/jbc.M505568200","article-title":"Tyrosine Phosphorylation of VE-cadherin Prevents Binding of p120- and \u03b2-Catenin and Maintains the Cellular Mesenchymal State","volume":"280","author":"MD Potter","year":"2005","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"pone.0231739.ref049","doi-asserted-by":"crossref","first-page":"H162","DOI":"10.1152\/ajpheart.00650.2010","article-title":"Phosphorylation of VE-cadherin controls endothelial phenotypes via p120-catenin coupling and Rac1 activation","volume":"300","author":"K Hatanaka","year":"2010","journal-title":"American Journal of Physiology\u2014Heart and Circulatory Physiology"},{"issue":"2","key":"pone.0231739.ref050","doi-asserted-by":"crossref","first-page":"e4449","DOI":"10.1371\/journal.pone.0004449","article-title":"The Integrin Antagonist Cilengitide Activates \u03b1V\u03b23, Disrupts VE-Cadherin Localization at Cell Junctions and Enhances Permeability in Endothelial Cells","volume":"4","author":"GC Alghisi","year":"2009","journal-title":"PLoS ONE"},{"issue":"1","key":"pone.0231739.ref051","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mvr.2011.04.005","article-title":"Interplay between FAK, PKC\u03b4, and p190RhoGAP in the Regulation of Endothelial Barrier Function","volume":"83","author":"KL Grinnell","year":"2012","journal-title":"Microvascular research"},{"issue":"3","key":"pone.0231739.ref052","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1083\/jcb.131.3.791","article-title":"Integrin function: molecular hierarchies of cytoskeletal and signaling molecules","volume":"131","author":"S Miyamoto","year":"1995","journal-title":"The Journal of Cell Biology"},{"issue":"9","key":"pone.0231739.ref053","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1242\/bio.017558","article-title":"Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation","volume":"5","author":"AL Roa-Espitia","year":"2016","journal-title":"Biology Open"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0231739","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T14:07:27Z","timestamp":1696082847000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0231739"}},"subtitle":[],"editor":[{"given":"Yulia","family":"Komarova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,4,30]]},"references-count":53,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0231739","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,30]]}}}