http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#Head http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://www.nanopub.org/nschema#hasAssertion http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#assertion http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://www.nanopub.org/nschema#hasProvenance http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#provenance http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://www.nanopub.org/nschema#hasPublicationInfo http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#pubinfo http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.nanopub.org/nschema#Nanopublication http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#assertion http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_1 http://purl.obolibrary.org/obo/RO_0002204 http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=1764 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_1 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_36080 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_2 http://purl.obolibrary.org/obo/BFO_0000066 http://purl.obolibrary.org/obo/UBERON_0002048 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_2 http://purl.obolibrary.org/obo/BFO_0000066 http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=9606 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#object http://amigo.geneontology.org/amigo/term/GO:0007155 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#predicate http://www.selventa.com/vocabulary/increases http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#subject http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_1 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_2 http://www.w3.org/1999/02/22-rdf-syntax-ns#type http://www.w3.org/1999/02/22-rdf-syntax-ns#Statement http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#assertion http://www.w3.org/2000/01/rdf-schema#label p(HGNC:CDH5) -> bp(GOBP:"cell adhesion") http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#provenance http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 61,000 statements. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_4 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_3 http://www.w3.org/ns/prov#value A complex interplay exists among these processes in regulating MLC phosphorylation status, cell tension, and subsequent EC permeability. Continued exploration of these pathways should provide additional important insights into the regulation of EC barrier function. Despite the clear contribution of MLCK/Rho kinase-driven increases in MLC phosphorylation to tension development and increased vascular permeability, MLCK-independent pathways are also involved in the regulation of cellular contraction (Fig. 4). Protein kinase C (PKC)-mediated pathways exert a prominent effect on barrier regulation in a time- and species-specific manner. For example, phorbol myristate acetate induces a PKC-dependent increase in bovine pulmonary EC permeability without significantly increasing MLC phosphorylation and without inducing formation of actin stress fibers, whereas PKC activation in human umbilical vein ECs does not have this barrier-disrupting effect (19, 50, 134), likely reflecting differences in PKC isotype-specific expression in the two species. PKC-mediated increases in bovine EC permeability may occur through phosphorylation of caldesmon, an actin-, myosin-, and CaM-binding protein present in smooth muscle actomyosin cross bridges as a 145-kDa protein and in EC as a 77-kDa protein (134). The phosphorylation of caldesmon is known to alter smooth muscle cross-bridge activity (93). Caldesmon distributes along stress fibers and is phosphorylated in EC after thrombin and phorbol myristate acetate challenge (134). Caldesmon-mediated regulation of actomyosin ATPase in smooth muscle is also modified by the actin cross-linking protein filamin and gelsolin (Table 1) (66). Although filamin participates directly in barrier regulation via CaM kinase II activation (14), its effects on actin cytoskeletal rearrangement are regulated through Rho family GTPases (6, 106), thereby providing another link with a known modulator of EC barrier function. Tumor necrosis factor- (TNF-) slowly induces barrier disruption in cultured EC, which is independent of MLCK activity (115). Finally, p38 kinase activation has also been linked to contractile regulation in smooth muscle (90), EC migration (97, 121), and lipopolysaccharide-induced EC permeability (164). The mechanism through which p38 exerts these effects is unclear but may involve the actin binding protein HSP27 (162), a known p38 MAPK target whose actin polymerization-inhibiting activity dramatically decreases after phosphorylation (7, 45) in association with stress fiber development (121, 126). ADHESIVE PROTEIN-CYTOSKELETON LINKAGES Cell-cell and cell-matrix adhesions are essential for barrier maintenance and restoration and exist in dynamic equilibrium with EC contractile forces. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes, adherens junctions and tight junctions, which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell (152). Adherens junctions are composed of cadherins bound together in a homotypic and Ca2+-dependent fashion to link adjacent EC (81). Cadherins interact through their cytoplasmic tail with the catenin family of intracellular proteins, which in turn provide anchorage to the actin cytoskeleton (1). The primary adhesive protein present in human endothelial adherens junctions, vascular endothelial (VE) cadherin (29), is critical to maintenance of EC barrier integrity as demonstrated by increased vascular permeability induced in mice after infusion of VE-cadherin-blocking antibody (25). http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11568129 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11568129 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#_3 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI#pubinfo http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://purl.org/dc/terms/created 2014-07-03T14:31:43.702+02:00 http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAV8Ck3OmO8h6HVP6RamVXrQbwh9APHGyJEp7yrs97AbI http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234