The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway

Alice J. Chen, Guisheng Zhou, Todd Juan, Suzanne M. Colicos, John P. Cannon, Maria Cabriera-Hansen, Christian F. Meyer, Roland Jurecic, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Fred Fletcher, Tse Hua Tan, John W. Belmont

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Abstract

The involvement of dual specificity phosphatases (DSPs) in the mitogen-activated protein kinase (MAPK) signaling has been mostly limited to the inactivation of MAPKs by the direct dephosphorylation of the TXY motif within their activation loop. We report the cloning and characterization of a murine DSP, called JNK pathway-associated phosphatase (JKAP), which lacks the regulatory region present in most other MAP kinase phosphatases (MKPs) and is preferentially expressed in murine Lin-Sca-1+ stem cells. Overexpression of JKAP in human embryonic kidney 293T cells specifically activated c-Jun N-terminal kinase (JNK) but not p38 and extracellular signal-regulated kinase 2. Overexpression of a mutant JKAP, JKAP-C88S, blocked tumor necrosis factor-α-induced JNK activation. Targeted gene disruption in murine embryonic stem cells abolished JNK activation by tumor necrosis factor-a and transforming growth factor-β, but not by ultraviolet-C irradiation, indicating that JKAP is necessary for optimal JNK activation. JKAP associated with JNK and MKK7, but not SEK1, in vivo. However, JKAP did not interact with JNK in vitro, suggesting that JKAP exerts its effect on JNK in an indirect manner. Taken together, these studies identify a positive regulator for the JNK pathway and suggest a novel role for DSP in mitogen-activated protein kinase regulation.

Original languageEnglish
Pages (from-to)36592-36601
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number39
DOIs
StatePublished - Sep 27 2002

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MAP Kinase Signaling System
JNK Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Dual-Specificity Phosphatases
Chemical activation
Mitogen-Activated Protein Kinases
Stem cells
Tumor Necrosis Factor-alpha
HEK293 Cells
Cloning
Nucleic Acid Regulatory Sequences
Mitogen-Activated Protein Kinase 1
Transforming Growth Factors
Embryonic Stem Cells
Organism Cloning
Phosphotransferases
Stem Cells
Genes
Irradiation
Kidney

ASJC Scopus subject areas

  • Biochemistry

Cite this

Chen, A. J., Zhou, G., Juan, T., Colicos, S. M., Cannon, J. P., Cabriera-Hansen, M., ... Belmont, J. W. (2002). The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway. Journal of Biological Chemistry, 277(39), 36592-36601. https://doi.org/10.1074/jbc.M200453200

The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway. / Chen, Alice J.; Zhou, Guisheng; Juan, Todd; Colicos, Suzanne M.; Cannon, John P.; Cabriera-Hansen, Maria; Meyer, Christian F.; Jurecic, Roland; Copeland, Neal G.; Gilbert, Debra J.; Jenkins, Nancy A.; Fletcher, Fred; Tan, Tse Hua; Belmont, John W.

In: Journal of Biological Chemistry, Vol. 277, No. 39, 27.09.2002, p. 36592-36601.

Research output: Contribution to journalArticle

Chen, AJ, Zhou, G, Juan, T, Colicos, SM, Cannon, JP, Cabriera-Hansen, M, Meyer, CF, Jurecic, R, Copeland, NG, Gilbert, DJ, Jenkins, NA, Fletcher, F, Tan, TH & Belmont, JW 2002, 'The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway', Journal of Biological Chemistry, vol. 277, no. 39, pp. 36592-36601. https://doi.org/10.1074/jbc.M200453200
Chen AJ, Zhou G, Juan T, Colicos SM, Cannon JP, Cabriera-Hansen M et al. The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway. Journal of Biological Chemistry. 2002 Sep 27;277(39):36592-36601. https://doi.org/10.1074/jbc.M200453200
Chen, Alice J. ; Zhou, Guisheng ; Juan, Todd ; Colicos, Suzanne M. ; Cannon, John P. ; Cabriera-Hansen, Maria ; Meyer, Christian F. ; Jurecic, Roland ; Copeland, Neal G. ; Gilbert, Debra J. ; Jenkins, Nancy A. ; Fletcher, Fred ; Tan, Tse Hua ; Belmont, John W. / The dual specificity JKAP specifically activates the c-Jun N-terminal kinase pathway. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 39. pp. 36592-36601.
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