Inactivation of jNK ACtivity by mitogen-activated protein kinase phosphatase-2 in Eahy926 endothelial cells is dependent upon agonist-specific jNK translocation to the nucleus

C. Robinson, C.M. Sloss, R.J. Plevin

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Abstract

We have investigated the termination of agonist-stimulated mitogen-activated protein (MAP) kinase activity in EAhy926 cells by MAP kinase phosphatase-2 (MKP-2). In cells expressing either wild-type (WT) or catalytically inactive (CI)-MKP-2, there was no significant differences in TNFα-stimulated JNK or p38 MAP kinase activity, however hydrogen peroxide (H2O2)-stimulated JNK activity was substantially reduced in WT-MKP-2 expressing clones and enhanced in cells expressing CI-MKP-2. Consistent with these findings, we observed substantial nuclear translocation of JNK occurred in response to H2O2 but not TNFα. Using a phosphospecific anti-JNK antibody, we found that TNFα-stimulated JNK activity was associated principally with the cytosol while in response to H2O2, JNK activity was found within the nucleus. These results show that the role of MKP-2 in terminating JNK activity is determined by the translocation of JNK to the nucleus, which is under agonist-specific regulation and not a universal cellular response to stimulation.
LanguageEnglish
Pages29-41
Number of pages13
JournalCellular Signalling
Volume13
Issue number1
DOIs
Publication statusPublished - 2001

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Mitogen-Activated Protein Kinase Phosphatases
Protein Phosphatase 2
Mitogen-Activated Protein Kinase 1
Phosphoric Monoester Hydrolases
Endothelial Cells
Phospho-Specific Antibodies
p38 Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Cytosol
Hydrogen Peroxide
Anti-Idiotypic Antibodies
Clone Cells

Keywords

  • protein kinase
  • endothelial cells
  • translocation

Cite this

@article{5697137d06604e53a104b858dc5dce46,
title = "Inactivation of jNK ACtivity by mitogen-activated protein kinase phosphatase-2 in Eahy926 endothelial cells is dependent upon agonist-specific jNK translocation to the nucleus",
abstract = "We have investigated the termination of agonist-stimulated mitogen-activated protein (MAP) kinase activity in EAhy926 cells by MAP kinase phosphatase-2 (MKP-2). In cells expressing either wild-type (WT) or catalytically inactive (CI)-MKP-2, there was no significant differences in TNFα-stimulated JNK or p38 MAP kinase activity, however hydrogen peroxide (H2O2)-stimulated JNK activity was substantially reduced in WT-MKP-2 expressing clones and enhanced in cells expressing CI-MKP-2. Consistent with these findings, we observed substantial nuclear translocation of JNK occurred in response to H2O2 but not TNFα. Using a phosphospecific anti-JNK antibody, we found that TNFα-stimulated JNK activity was associated principally with the cytosol while in response to H2O2, JNK activity was found within the nucleus. These results show that the role of MKP-2 in terminating JNK activity is determined by the translocation of JNK to the nucleus, which is under agonist-specific regulation and not a universal cellular response to stimulation.",
keywords = "protein kinase , endothelial cells , translocation",
author = "C. Robinson and C.M. Sloss and R.J. Plevin",
year = "2001",
doi = "10.1016/S0898-6568(00)00121-2",
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TY - JOUR

T1 - Inactivation of jNK ACtivity by mitogen-activated protein kinase phosphatase-2 in Eahy926 endothelial cells is dependent upon agonist-specific jNK translocation to the nucleus

AU - Robinson, C.

AU - Sloss, C.M.

AU - Plevin, R.J.

PY - 2001

Y1 - 2001

N2 - We have investigated the termination of agonist-stimulated mitogen-activated protein (MAP) kinase activity in EAhy926 cells by MAP kinase phosphatase-2 (MKP-2). In cells expressing either wild-type (WT) or catalytically inactive (CI)-MKP-2, there was no significant differences in TNFα-stimulated JNK or p38 MAP kinase activity, however hydrogen peroxide (H2O2)-stimulated JNK activity was substantially reduced in WT-MKP-2 expressing clones and enhanced in cells expressing CI-MKP-2. Consistent with these findings, we observed substantial nuclear translocation of JNK occurred in response to H2O2 but not TNFα. Using a phosphospecific anti-JNK antibody, we found that TNFα-stimulated JNK activity was associated principally with the cytosol while in response to H2O2, JNK activity was found within the nucleus. These results show that the role of MKP-2 in terminating JNK activity is determined by the translocation of JNK to the nucleus, which is under agonist-specific regulation and not a universal cellular response to stimulation.

AB - We have investigated the termination of agonist-stimulated mitogen-activated protein (MAP) kinase activity in EAhy926 cells by MAP kinase phosphatase-2 (MKP-2). In cells expressing either wild-type (WT) or catalytically inactive (CI)-MKP-2, there was no significant differences in TNFα-stimulated JNK or p38 MAP kinase activity, however hydrogen peroxide (H2O2)-stimulated JNK activity was substantially reduced in WT-MKP-2 expressing clones and enhanced in cells expressing CI-MKP-2. Consistent with these findings, we observed substantial nuclear translocation of JNK occurred in response to H2O2 but not TNFα. Using a phosphospecific anti-JNK antibody, we found that TNFα-stimulated JNK activity was associated principally with the cytosol while in response to H2O2, JNK activity was found within the nucleus. These results show that the role of MKP-2 in terminating JNK activity is determined by the translocation of JNK to the nucleus, which is under agonist-specific regulation and not a universal cellular response to stimulation.

KW - protein kinase

KW - endothelial cells

KW - translocation

U2 - 10.1016/S0898-6568(00)00121-2

DO - 10.1016/S0898-6568(00)00121-2

M3 - Article

VL - 13

SP - 29

EP - 41

JO - Cellular Signalling

T2 - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

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ER -