Activation-independent nuclear translocation of mitogen activated protein kinase ERK1 mediated by thiol-modifying chemicals.
The extracellular signal-regulated kinases ERK1 and ERK2 are key mediators of mitogenic signals in most cell types. In fibroblasts, sustained activation and nuclear translocation are mandatory for S-phase induction. The events leading to activation of these kinases are well understood, whereas little is known about the mechanism of their translocation. Using indirect immunofluorescence and biochemical analysis we show that ERK1 can translocate to the nucleus in the absence of activation and phosphorylation by upstream kinases when cells are treated with thiol-modifying chemicals. We propose that these chemicals inactivate a protein contributing to the cytoplasmic localization of ERK1.
Meili
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Friedrich Miescher Institute, Basel, Switzerland.
Ballmer-Hofer
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D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004789:Enzyme Activation; D005033:Ethylmaleimide / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D008870:Microtubules / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D016196:S Phase; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D014404:Tubulin / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
D001152:Arsenicals; D010982:Platelet-Derived Growth Factor; D013439:Sulfhydryl Reagents; D014404:Tubulin; C076715:pervanadate; C029341:oxophenylarsine; D014638:Vanadates; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; D005033:Ethylmaleimide