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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#_7 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#_6 http://www.w3.org/ns/prov#value We generated transgenic mice that overexpress the human disease-associated K8 Gly61-to-Cys (G61C) variant and showed that G61C predisposes to liver injury and apoptosis and dramatically inhibits K8 phosphorylation at serine 73 (S73) via stress-activated kinases. This led us to generate mice that overexpress K8 S73-to-Ala (S73A), which mimicked the susceptibility of K8 G61C mice to injury, thereby providing a molecular link between K8 phosphorylation and disease-associated mutation. Upon apoptotic stimulation, G61C and S73A hepatocytes have persistent and increased nonkeratin proapoptotic substrate phosphorylation by stress-activated kinases, compared with wild-type hepatocytes, in association with an inability to phosphorylate K8 S73. Our findings provide the first direct link between patient-related human keratin variants and liver disease predisposition. The highly abundant cytoskeletal protein K8, and possibly other keratins with the conserved S73-containing phosphoepitope, can protect tissue from injury by serving as a phosphate \"sponge\" for stress-activated kinases and thereby provide a novel nonmechanical function for intermediate filament proteins. http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#_6 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/16818723 http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#_7 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/16818723 http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#_6 http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc#pubinfo http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc http://purl.org/dc/terms/created 2014-07-03T14:30:43.899+02:00 http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAb5fCrZHrSyPdl0jx2JMw9u9Y4YM03uN-yrlAZqzG7sc http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234