The JNK phosphatase M3/6 is inhibited by protein-damaging stress.
Cells respond to stresses such as osmotic shock and heat shock by activating stress-activated protein kinases (SAPKs), including c-Jun N-terminal kinase (JNK) [1]. Activation of JNK requires phosphorylation of threonine and tyrosine residues in the TPY activation loop motif [2, 3] and can be reversed by the removal of either phosphate group. Numerous JNK phosphatases including dual-specificity phosphatases [4, 5], have been identified. Many stimuli activate JNK by increasing its rate of phosphorylation; however, JNK dephosphorylation is inhibited in cells after heat shock [6], suggesting that a JNK phosphatase(s) is inactivated. M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]. We have previously expressed M3/6 in the mouse bone marrow cell line BAF3 in order to show that JNK activation by IL-3 is necessary for cell survival and proliferation [9]. Here we report that M3/6 dissociates from JNK and appears in an insoluble fraction after heat shock. These data identify M3/6 as a JNK phosphatase that is inactivated by heat shock and provide a molecular mechanism for the activation of JNK by heat shock.
Palacios
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The Department of Immunology, University College London Medical School, Windeyer Building, 46 Cleveland Street, London W1P6DB, United Kingdom.
Collins
M K
MK
Perkins
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GR
D054637:Dual-Specificity Phosphatases; D006361:Heating; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012995:Solubility
D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C517038:DUSP8 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases