Logo image
RANTES-mediated chemokine transcription in astrocytes involves activation and translocation of p90 ribosomal S6 protein kinase (RSK)
Journal article   Open access   Peer reviewed

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 Dorf
The Journal of biological chemistry, Vol.277(21), pp.19042-19048
05/24/2002
DOI: 10.1074/jbc.M112442200
PMID: 11893739
url
https://doi.org/10.1074/jbc.M112442200View
Published (Version of record) Open Access

Abstract

RANTES (regulated on activation normal T cell expressed and secreted) (> or =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.
Animals Astrocytes - enzymology Astrocytes - metabolism Chemokine CCL5 - physiology Chemokines - genetics Enzyme Activation Enzyme-Linked Immunosorbent Assay MAP Kinase Signaling System Mice Mice, Inbred BALB C Phosphorylation Protein Transport Recombinant Proteins - metabolism Ribosomal Protein S6 Kinases - metabolism Transcription, Genetic - physiology Tumor Necrosis Factor-alpha - biosynthesis

Details

Metrics

Logo image