Differential effects of stress stimuli on a JNK-inactivating phosphatase.
Stress signals elicit a wide variety of cellular responses, many of which converge on the phosphorylation of JNK and p38 kinases, the activation of which has been well-characterized. How these kinases are switched off by dephosphorylation is not well understood. Here we describe how diverse cellular stresses affect differently the stability and activity of a JNK-inactivating dual-specificity threonine-tyrosine phosphatase M3/6. Both anisomycin and arsenite activate the JNK pathway and, in addition, inactivate the M3/6 phosphatase. However, while anisomycin treatment of cells leads to M3/6 protein degradation, arsenite appears to inactivate M3/6 directly. These results might have implications for the mechanism of tumour promotion by arsenic.
Theodosiou
Aspasia
A
CRC Gene Function and Regulation Group, The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Ashworth
Alan
A
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000841:Anisomycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D002461:Cell Line, Transformed; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D054637:Dual-Specificity Phosphatases; D004795:Enzyme Stability / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010750:Phosphoproteins / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018053:Arsenites; D015853:Cysteine Proteinase Inhibitors; D010750:Phosphoproteins; C067713:lactacystin; D000841:Anisomycin; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C517038:DUSP8 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases; C015001:arsenite; D000111:Acetylcysteine