PubMed:9786869 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/9786869","sourcedb":"PubMed","sourceid":"9786869","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9786869","text":"Cleavage and activation of p21-activated protein kinase gamma-PAK by CPP32 (caspase 3). Effects of autophosphorylation on activity.\np21-activated protein kinase gamma-PAK (Pak2, PAK I) is cleaved by CPP32 (caspase 3) during apoptosis and plays a key role in regulation of cell death. In vitro, CPP32 cleaves recombinant gamma-PAK into two peptides; 1-212 contains the majority of the regulatory domain whereas 213-524 contains 34 amino acids of the regulatory domain plus the entire catalytic domain. Following cleavage, both peptides become autophosphorylated with [gamma-32P]ATP. Peptide 1-212 migrates at 27,000 daltons (p27) upon SDS-polyacrylamide gel electrophoresis and at 32,000 daltons following autophosphorylation on serine (p27P); the catalytic subunit migrates at 34,000 daltons (p34) before and after autophosphorylation on threonine. Following caspase cleavage, a significant lag (approximately 5 min) is observed before autophosphorylation and activity are detected. When gamma-PAK is autophosphorylated with ATP(Mg) alone and then cleaved, only p27 contains phosphate, and the enzyme is inactive with exogenous substrate. After autophosphorylation of gamma-PAK in the presence of Cdc42(GTPgammaS) or histone 4, both cleavage products contain phosphate and gamma-PAK is catalytically active. Mutation of the conserved Thr-402 to alanine greatly reduces autophosphorylation and protein kinase activity following cleavage. Thus activation of gamma-PAK via cleavage by CPP32 is a two-step mechanism wherein autophosphorylation of the regulatory domain is a priming step, and activation coincides with autophosphorylation of the catalytic domain.","tracks":[{"project":"GlyCosmos6-UBERON","denotations":[{"id":"T1","span":{"begin":272,"end":276},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"subj":"T1","pred":"source","obj":"GlyCosmos6-UBERON"}]},{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":87},"obj":"Sentence"},{"id":"T2","span":{"begin":88,"end":131},"obj":"Sentence"},{"id":"T3","span":{"begin":132,"end":283},"obj":"Sentence"},{"id":"T4","span":{"begin":284,"end":500},"obj":"Sentence"},{"id":"T5","span":{"begin":501,"end":581},"obj":"Sentence"},{"id":"T6","span":{"begin":582,"end":848},"obj":"Sentence"},{"id":"T7","span":{"begin":849,"end":982},"obj":"Sentence"},{"id":"T8","span":{"begin":983,"end":1138},"obj":"Sentence"},{"id":"T9","span":{"begin":1139,"end":1307},"obj":"Sentence"},{"id":"T10","span":{"begin":1308,"end":1436},"obj":"Sentence"},{"id":"T11","span":{"begin":1437,"end":1658},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"}]},{"project":"GlyCosmos6-CLO","denotations":[{"id":"T1","span":{"begin":13,"end":23},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T2","span":{"begin":31,"end":40},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T3","span":{"begin":122,"end":130},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T4","span":{"begin":136,"end":145},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T5","span":{"begin":272,"end":276},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T6","span":{"begin":960,"end":968},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T7","span":{"begin":1300,"end":1306},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T8","span":{"begin":1408,"end":1416},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T9","span":{"begin":1442,"end":1452},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"},{"id":"T10","span":{"begin":1588,"end":1598},"obj":"http://purl.obolibrary.org/obo/CLO_0001658"}],"attributes":[{"subj":"T1","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T2","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T3","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T4","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T5","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T6","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T7","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T8","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T9","pred":"source","obj":"GlyCosmos6-CLO"},{"subj":"T10","pred":"source","obj":"GlyCosmos6-CLO"}]},{"project":"2015-BEL-Sample","denotations":[{"id":"T1","span":{"begin":71,"end":283},"obj":"cat(p(HGNC:CASP3)) directlyIncreases kin(p(HGNC:PAK2))"}],"attributes":[{"subj":"T1","pred":"source","obj":"2015-BEL-Sample"}]},{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20000042","span":{"begin":71,"end":283},"obj":"cat(p(HGNC:CASP3)) directlyIncreases kin(p(HGNC:PAK2))"},{"id":"BEL:20000042","span":{"begin":71,"end":282},"obj":"cat(p(HGNC:CASP3)) directlyIncreases kin(p(HGNC:PAK2))"},{"id":"BEL:20001174","span":{"begin":132,"end":499},"obj":"cat(p(HGNC:CASP3)) directlyIncreases kin(p(HGNC:PAK2))"}],"attributes":[{"subj":"BEL:20000042","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20000042","pred":"source","obj":"2015-BEL-Sample-2"},{"subj":"BEL:20001174","pred":"source","obj":"2015-BEL-Sample-2"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"GlyCosmos6-UBERON","color":"#93eaec","default":true},{"id":"sentences","color":"#ecd493"},{"id":"GlyCosmos6-CLO","color":"#b993ec"},{"id":"2015-BEL-Sample","color":"#93ec9f"},{"id":"2015-BEL-Sample-2","color":"#ec93a0"}]}]}}