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Originally published In Press as doi:10.1074/jbc.M112442200 on March 13, 2002

J. Biol. Chem., Vol. 277, Issue 21, 19042-19048, May 24, 2002
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RANTES-mediated Chemokine Transcription in Astrocytes Involves Activation and Translocation of p90 Ribosomal S6 Protein Kinase (RSK)*

Ye Zhang, Qiwei Zhai, Yi Luo, and Martin E. DorfDagger

From the Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

RANTES (regulated on activation normal T cell expressed and secreted) (>= 10 ng/ml) stimulates the induction of KC and other chemokines in astrocytes. Elements of the signal transduction pathway controlling this response were identified. RANTES induced phosphorylation of MEK, ERK1/2, p90 ribosomal S6 kinases (RSK), and cAMP-response element-binding protein (CREB) in astrocytes. U0126, a pharmacological inhibitor of MEK, blocked the phosphorylation of the downstream elements ERK, RSK, and CREB, inhibited chemokine synthesis, and reduced transcription from a KC promoter construct. Dominant negative mutants of RSK or CREB blocked the transcription driven by the KC promoter. Finally, RANTES treatment induces nuclear translocation of phosphorylated RSK in astrocytes. This novel role for RSK in signaling chemokine responses and synthesis in astrocytes may contribute to the amplification mechanisms responsible for prolonging inflammatory responses in the central nervous system.

* This study was supported in part by National Institutes of Health Grants NS37284 and CA67416 and a grant from the Hoechst Marion Roussel Collaboration.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Pathology, Harvard Medical School, Armenise Bldg. D530, 200 Longwood Ave., Boston, MA 02115. Tel.: 617-432-1978; Fax: 617-432-2789; E-mail: dorf@hms.harvard.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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