Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 98 (24): 13613-13618

Copyright © 2001 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / BIOCHEMISTRY

Activation of the Jnk signaling pathway by a dual-specificity phosphatase, JSP-1

Yu Shen*, Ralf Luche{dagger}, Bo Wei{dagger}, Marcia L. Gordon{dagger}, Curtis D. Diltz{dagger}, and Nicholas K. Tonks*,{ddagger}

*Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and {dagger}CEPTYR, Incorporated, Bothell, WA 98021

Accepted for publication September 21, 2001.

Received for publication June 5, 2001.

Abstract: The mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli, such as growth factors, hormones, and cytokines, and to a wide variety of environmental stresses. The MAPKs, which are stimulated by phosphorylation of a TXY motif in their activation loop, are components of signal transduction cascades in which sequential activation of protein kinases culminates in their activation and their subsequent phosphorylation of various effector proteins that mediate the physiological response. MAPKs are also subject to dephosphorylation and inactivation, both by enzymes that recognize the residues of the TXY motif independently and by dual specificity phosphatases, which dephosphroylate both Tyr and Ser/Thr residues. We report the identification and characterization of a novel dual specificity phosphatase. Contrary to expectation, this broadly expressed enzyme did not inactivate MAPKs in transient cotransfection assays but instead displayed the capacity to function as a selective activator of the MAPK Jnk, hence the name, Jnk Stimulatory Phosphatase-1 (JSP-1). This study illustrates a new aspect of the regulation of MAPK-dependent signal transduction and raises the possibility that JSP-1 may offer a different perspective to the study of various inflammatory and proliferative disorders associated with dysfunctional Jnk signaling.


{ddagger} To whom reprint requests should be addressed at: Cold Spring Harbor Laboratory, Demerec Building, 1 Bungtown Road, Cold Spring Harbor, NY 11724-2208. E-mail: tonks{at}cshl.org.

Communicated by Michael H. Wigler, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF424702).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
MEKK2 Kinase Association with 14-3-3 Protein Regulates Activation of c-Jun N-terminal Kinase.
A. E. Matitau, T. V. Gabor, R. M. Gill, and M. P. Scheid (2013)
J. Biol. Chem. 288, 28293-28302
   Abstract »    Full Text »    PDF »
Preliminary Evidence for Leukocyte Transcriptional Signatures for Pediatric Ventilator-Associated Pneumonia.
J. A. Werner, W. Schierding, D. Dixon, S. MacMillan, D. Oppedal, J. Muenzer, J. P. Cobb, and P. A. Checchia (2012)
J Intensive Care Med 27, 362-369
   Abstract »    Full Text »    PDF »
JNK Pathway-associated Phosphatase Dephosphorylates Focal Adhesion Kinase and Suppresses Cell Migration.
J.-P. Li, Y.-N. Fu, Y.-R. Chen, and T.-H. Tan (2010)
J. Biol. Chem. 285, 5472-5478
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer.
T. Boutros, E. Chevet, and P. Metrakos (2008)
Pharmacol. Rev. 60, 261-310
   Abstract »    Full Text »    PDF »
DUSP Meet Immunology: Dual Specificity MAPK Phosphatases in Control of the Inflammatory Response.
R. Lang, M. Hammer, and J. Mages (2006)
J. Immunol. 177, 7497-7504
   Abstract »    Full Text »    PDF »
Active ERK Contributes to Protein Translation by Preventing JNK-Dependent Inhibition of Protein Phosphatase 1.
M. M. Monick, L. S. Powers, T. J. Gross, D. M. Flaherty, C. W. Barrett, and G. W. Hunninghake (2006)
J. Immunol. 177, 1636-1645
   Abstract »    Full Text »    PDF »
Characterization of Two Distinct Dual Specificity Phosphatases Encoded in Alternative Open Reading Frames of a Single Gene Located on Human Chromosome 10q22.2.
H.-H. Chen, R. Luche, B. Wei, and N. K. Tonks (2004)
J. Biol. Chem. 279, 41404-41413
   Abstract »    Full Text »    PDF »
VHY, a Novel Myristoylated Testis-restricted Dual Specificity Protein Phosphatase Related to VHX.
A. Alonso, S. Narisawa, J. Bogetz, L. Tautz, R. Hadzic, H. Huynh, S. Williams, A. Gjorloff-Wingren, M. C. D. Bremer, L. J. Holsinger, et al. (2004)
J. Biol. Chem. 279, 32586-32591
   Abstract »    Full Text »    PDF »
A Role for Protein Phosphatase-2A in p38 Mitogen-activated Protein Kinase-mediated Regulation of the c-Jun NH2-terminal Kinase Pathway in Human Neutrophils.
N. J. Avdi, K. C. Malcolm, J. A. Nick, and G. S. Worthen (2002)
J. Biol. Chem. 277, 40687-40696
   Abstract »    Full Text »    PDF »
The Dual Specificity JKAP Specifically Activates the c-Jun N-terminal Kinase Pathway.
A. J. Chen, G. Zhou, T. Juan, S. M. Colicos, J. P. Cannon, M. Cabriera-Hansen, C. F. Meyer, R. Jurecic, N. G. Copeland, D. J. Gilbert, et al. (2002)
J. Biol. Chem. 277, 36592-36601
   Abstract »    Full Text »    PDF »
A Novel Dual Specificity Phosphatase SKRP1 Interacts with the MAPK Kinase MKK7 and Inactivates the JNK MAPK Pathway. IMPLICATION FOR THE PRECISE REGULATION OF THE PARTICULAR MAPK PATHWAY.
T. Zama, R. Aoki, T. Kamimoto, K. Inoue, Y. Ikeda, and M. Hagiwara (2002)
J. Biol. Chem. 277, 23909-23918
   Abstract »    Full Text »    PDF »
Scaffold Role of a Mitogen-activated Protein Kinase Phosphatase, SKRP1, for the JNK Signaling Pathway.
T. Zama, R. Aoki, T. Kamimoto, K. Inoue, Y. Ikeda, and M. Hagiwara (2002)
J. Biol. Chem. 277, 23919-23926
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882