Preheating accelerates mitogen-activated protein (MAP) kinase inactivation post-heat shock via a heat shock protein 70-mediated increase in phosphorylated MAP kinase phosphatase-1.
Heat shock (HS) activates mitogen-activated protein (MAP) kinases. Although prior exposure to nonlethal HS makes cells refractory to the lethal effect of a subsequent HS, it is unclear whether this also occurs in MAP kinase activation. This study was undertaken to evaluate the effect of a heat pretreatment on MAP ... kinase activation by a subsequent HS and to elucidate its possible mechanism. Preheating did not make BEAS-2B cells refractory to extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) activation by a second HS but accelerated their inactivation after HS. The rapid inactivation of ERK and JNK was dependent on de novo protein synthesis and associated with the up-regulation of heat shock protein 70 (HSP70). Moreover, the inhibition of phosphatase activity reversed this rapid inactivation. MAP kinase phosphatase-1 (MKP-1) expression was increased by HS, and the presence of its phosphorylated form (p-MKP-1) correlated with the observed rapid ERK and JNK inactivation. Blocking induction of p-MKP-1 with antisense MKP-1 oligonucleotides suppressed the rapid inactivation of ERK and JNK in preheated cells. HSP70 overexpression caused the early phosphorylation of MKP-1. Moreover, MKP-1 phosphorylation and the rapid inactivation of ERK were inhibited by blocking HSP70 induction in preheated cells. In addition, MKP-1 was insolubilized by HS, and HSP70 associated physically with MKP-1, suggesting that a chaperone effect of HSP70 might have caused the early phosphorylation of MKP-1. These results indicate that preheating accelerated MAP kinase inactivation after a second HS and that this is related to a HSP70-mediated increase in p-MKP-1.
Mesh Terms:
Adenoviridae, Animals, Blotting, Western, Bronchi, Cell Cycle Proteins, Cells, Cultured, Dual Specificity Phosphatase 1, Enzyme Inhibitors, Epithelial Cells, HSP70 Heat-Shock Proteins, Hot Temperature, Humans, Immediate-Early Proteins, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinase Kinases, NIH 3T3 Cells, Oligonucleotides, Oligonucleotides, Antisense, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Protein Phosphatase 1, Protein Tyrosine Phosphatases, Time Factors, Up-Regulation
Adenoviridae, Animals, Blotting, Western, Bronchi, Cell Cycle Proteins, Cells, Cultured, Dual Specificity Phosphatase 1, Enzyme Inhibitors, Epithelial Cells, HSP70 Heat-Shock Proteins, Hot Temperature, Humans, Immediate-Early Proteins, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinase Kinases, NIH 3T3 Cells, Oligonucleotides, Oligonucleotides, Antisense, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Protein Phosphatase 1, Protein Tyrosine Phosphatases, Time Factors, Up-Regulation
J. Biol. Chem.
Date: Apr. 01, 2005
PubMed ID: 15677475
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