The serine/threonine phosphatase, PP2A: Endogenous regulator of inflammatory cell signaling

T. P. Shanley*, N. Vasi, A. Denenberg, H. R. Wong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

We have investigated the regulation of kinases and phosphatases in early gene activation in monocytes because these cells are implicated in the pathogenesis of acute inflammatory states, such as sepsis and acute lung injury. One early gene up-regulated by endotoxin is c-Jun, a member of the activating protein (AP) family. C-Jun is phosphorylated by c-Jun N-terminal kinase (JNK) and associates with c-Fos to form the AP-1 transcriptional activation complex that can drive cytokine expression. Inhibition of the serine/threonine phosphatase, PP2-A, with okadaic acid resulted in a significant increase in JNK activity. This finding was associated with increased phosphorylation of c-Jun, AP-1 transcriptional activity, and IL-1β expression. Activation of PP2A inhibited JNK activity and JNK coprecipitaed with the regulatory subunit, PP2A-Aα, supporting the conclusion that PP2A is a key regulatory of JNK in the context of an inflammatory stimulus.

Original languageEnglish (US)
Pages (from-to)966-972
Number of pages7
JournalJournal of Immunology
Volume166
Issue number2
DOIs
StatePublished - Jan 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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