PubMed:10508167 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":49,"end":52},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":270,"end":273},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0012041"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0012041"}],"text":"Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer.\nIn response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK) translocates from the cytoplasm to the nucleus. MAP kinase kinase (MAPKK, also know as MEK), which possesses a nuclear export signal (NES), acts as a cytoplasmic anchor of MAPK. Here we show evidence that tyrosine (Tyr190 in Xenopus MPK1/ERK2) phosphorylation of MAPK by MAPKK is necessary and sufficient for the dissociation of the MAPKK-MAPK complex, and that the dissociation of the complex is required for the nuclear translocation of MAPK. We then show that nuclear entry of MAPK through a nuclear pore occurs via two distinct mechanisms. Nuclear import of wild-type MAPK (mol. wt 42 kDa) was induced by activation of the MAPK pathway even in the presence of wheat germ agglutinin or dominant-negative Ran, whereas nuclear import of beta-galactosidase (beta-gal)-fused MAPK (mol. wt 160 kDa), which occurred in response to stimuli, was completely blocked by these inhibitors. Moreover, while a dimerization-deficient mutant of MAPK was able to translocate to the nucleus upon stimulation, this mutant MAPK, when fused to beta-gal, became unable to enter the nucleus. These results suggest that monomeric and dimeric forms of MAPK enter the nucleus by passive diffusion and active transport mechanisms, respectively."}

{"project":"bionlp-st-pc-2013-training","denotations":[{"id":"T1","span":{"begin":31,"end":38},"obj":"Cellular_component"},{"id":"T2","span":{"begin":49,"end":59},"obj":"Gene_or_gene_product"},{"id":"T3","span":{"begin":163,"end":195},"obj":"Gene_or_gene_product"},{"id":"T4","span":{"begin":197,"end":201},"obj":"Gene_or_gene_product"},{"id":"T5","span":{"begin":217,"end":220},"obj":"Gene_or_gene_product"},{"id":"T6","span":{"begin":244,"end":253},"obj":"Cellular_component"},{"id":"T7","span":{"begin":261,"end":268},"obj":"Cellular_component"},{"id":"T8","span":{"begin":270,"end":287},"obj":"Gene_or_gene_product"},{"id":"T9","span":{"begin":289,"end":294},"obj":"Gene_or_gene_product"},{"id":"T10","span":{"begin":309,"end":312},"obj":"Gene_or_gene_product"},{"id":"T11","span":{"begin":333,"end":340},"obj":"Cellular_component"},{"id":"T12","span":{"begin":372,"end":383},"obj":"Cellular_component"},{"id":"T13","span":{"begin":394,"end":398},"obj":"Gene_or_gene_product"},{"id":"T14","span":{"begin":427,"end":435},"obj":"Simple_chemical"},{"id":"T15","span":{"begin":437,"end":443},"obj":"Simple_chemical"},{"id":"T16","span":{"begin":455,"end":459},"obj":"Gene_or_gene_product"},{"id":"T17","span":{"begin":460,"end":464},"obj":"Gene_or_gene_product"},{"id":"T18","span":{"begin":485,"end":489},"obj":"Gene_or_gene_product"},{"id":"T19","span":{"begin":493,"end":498},"obj":"Gene_or_gene_product"},{"id":"T20","span":{"begin":555,"end":565},"obj":"Complex"},{"id":"T21","span":{"begin":636,"end":643},"obj":"Cellular_component"},{"id":"T22","span":{"begin":661,"end":665},"obj":"Gene_or_gene_product"},{"id":"T23","span":{"begin":685,"end":692},"obj":"Cellular_component"},{"id":"T24","span":{"begin":702,"end":706},"obj":"Gene_or_gene_product"},{"id":"T25","span":{"begin":717,"end":729},"obj":"Cellular_component"},{"id":"T26","span":{"begin":766,"end":773},"obj":"Cellular_component"},{"id":"T27","span":{"begin":794,"end":798},"obj":"Gene_or_gene_product"},{"id":"T28","span":{"begin":849,"end":853},"obj":"Gene_or_gene_product"},{"id":"T29","span":{"begin":897,"end":907},"obj":"Gene_or_gene_product"},{"id":"T30","span":{"begin":929,"end":932},"obj":"Gene_or_gene_product"},{"id":"T31","span":{"begin":942,"end":949},"obj":"Cellular_component"},{"id":"T32","span":{"begin":960,"end":978},"obj":"Gene_or_gene_product"},{"id":"T33","span":{"begin":980,"end":988},"obj":"Gene_or_gene_product"},{"id":"T34","span":{"begin":996,"end":1000},"obj":"Gene_or_gene_product"},{"id":"T35","span":{"begin":1154,"end":1158},"obj":"Gene_or_gene_product"},{"id":"T36","span":{"begin":1190,"end":1197},"obj":"Cellular_component"},{"id":"T37","span":{"begin":1228,"end":1232},"obj":"Gene_or_gene_product"},{"id":"T38","span":{"begin":1248,"end":1256},"obj":"Gene_or_gene_product"},{"id":"T39","span":{"begin":1285,"end":1292},"obj":"Cellular_component"},{"id":"T40","span":{"begin":1352,"end":1356},"obj":"Gene_or_gene_product"},{"id":"T41","span":{"begin":1367,"end":1374},"obj":"Cellular_component"}],"text":"Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer.\nIn response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK) translocates from the cytoplasm to the nucleus. MAP kinase kinase (MAPKK, also know as MEK), which possesses a nuclear export signal (NES), acts as a cytoplasmic anchor of MAPK. Here we show evidence that tyrosine (Tyr190 in Xenopus MPK1/ERK2) phosphorylation of MAPK by MAPKK is necessary and sufficient for the dissociation of the MAPKK-MAPK complex, and that the dissociation of the complex is required for the nuclear translocation of MAPK. We then show that nuclear entry of MAPK through a nuclear pore occurs via two distinct mechanisms. Nuclear import of wild-type MAPK (mol. wt 42 kDa) was induced by activation of the MAPK pathway even in the presence of wheat germ agglutinin or dominant-negative Ran, whereas nuclear import of beta-galactosidase (beta-gal)-fused MAPK (mol. wt 160 kDa), which occurred in response to stimuli, was completely blocked by these inhibitors. Moreover, while a dimerization-deficient mutant of MAPK was able to translocate to the nucleus upon stimulation, this mutant MAPK, when fused to beta-gal, became unable to enter the nucleus. These results suggest that monomeric and dimeric forms of MAPK enter the nucleus by passive diffusion and active transport mechanisms, respectively."}