Regulation of c-Jun NH2-terminal Kinase ( Jnk) Gene Expression during T Cell Activation

doi:10.1084/jem.191.1.139

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© The Rockefeller University Press, 0022-1007/2000/1/139/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 1, January 3, 2000 139-146

Original Article

Regulation of c-Jun NH₂-terminal Kinase ( Jnk) Gene Expression during T Cell Activation

Linda Weiss^a, Alan J. Whitmarsh^b, Derek D. Yang^c, Mercedes Rincón^a, Roger J. Davis^b, and Richard A. Flavell^c
^a Immunobiology Program, Department of Medicine, University of Vermont, Burlington, Vermont 05405
^b Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605
^c Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520

Correspondence to: Mercedes Rincón, Department of Medicine/Immunobiology Program, Given Medical Bldg. D-305, University of Vermont, Burlington, VT 05405. Tel:802-656-0937 Fax:802-656-3854 E-mail:mrincon{at}zoo.uvm.edu.

The c-Jun NH₂-terminal kinases (JNKs) are a group of mitogen-activatedprotein (MAP) kinases that participate in signal transductionevents mediating specific cellular functions. Activation ofJNK is regulated by phosphorylation in response to cellularstress and inflammatory cytokines. Here, we demonstrate thatJNK is regulated by a second, novel mechanism. Induction ofJnk gene expression is required in specific tissues before activationof this signaling pathway. The in vivo and in vitro ligationof the T cell receptor (TCR) leads to induction of JNK geneand protein expression. TCR signals are sufficient to induceJNK expression, whereas JNK phosphorylation also requires CD28-mediatedcostimulatory signals. Therefore, both expression and activationcontribute to the regulation of the JNK pathway to ensure propercontrol during the course of an immune response.

Key Words: c-Jun NH₂-terminal kinase, gene expression, T cells, phosphorylation,signal transduction

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