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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).

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