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Molecular and Cellular Biology, March 1999, p. 2021-2031, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Jun Kinase Phosphorylates and Regulates the DNA Binding Activity of an Octamer Binding Protein, T-Cell Factor beta 1dagger

Shailaja Kasibhatla,1 Pankaj Tailor,2 Nathalie Bonefoy-Berard,2 Tomas Mustelin,2 Amnon Altman,2 and Arun Fotedar1,3,*

Divisions of Molecular Biology1 and Cell Biology,2 La Jolla Institute for Allergy and Immunology, and Sidney Kimmel Cancer Center,3 San Diego, California 92121

Received 8 June 1998/Returned for modification 1 July 1998/Accepted 11 November 1998

POU domain proteins have been implicated as key regulators during development and lymphocyte activation. The POU domain protein T-cell factor beta 1 (TCFbeta 1), which binds octamer and octamer-related sequences, is a potent transactivator. In this study, we showed that TCFbeta 1 is phosphorylated following activation via the T-cell receptor or by stress-induced signals. Phosphorylation of TCFbeta 1 occurred predominantly at serine and threonine residues. Signals which upregulate Jun kinase (JNK)/stress-activated protein kinase activity also lead to association of JNK with TCFbeta 1. JNK associates with the activation domain of TCFbeta 1 and phosphorylates its DNA binding domain. The phosphorylation of recombinant TCFbeta 1 by recombinant JNK enhances the ability of TCFbeta 1 to bind to a consensus octamer motif. Consistent with this conclusion, TCFbeta 1 upregulates reporter gene transcription in an activation- and JNK-dependent manner. In addition, inhibition of JNK activity by catalytically inactive MEKK (in which methionine was substituted for the lysine at position 432) also inhibits the ability of TCFbeta 1 to drive inducible transcription from the interleukin-2 promoter. These results suggest that stress-induced signals and T-cell activation induce JNK, which then acts on multiple cis sequences by modulating distinct transactivators like c-Jun and TCFbeta 1. This demonstrates a coupling between the JNK activation pathway and POU domain proteins and implicates TCFbeta 1 as a physiological target in the JNK signal transduction pathway leading to coordinated biological responses.

* Corresponding author. Mailing address: Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121. Phone: (619) 450-5990. Fax: (619) 550-3998. E-mail: FOTEDAR{at}aol.com.

dagger Manuscript 138 from the La Jolla Institute for Allergy and Immunology.

Molecular and Cellular Biology, March 1999, p. 2021-2031, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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