Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes

Luo Sun, Hong Duk Youn, Christine Loh, Melissa Stolow, Weiwu He, Jun O. Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin I that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross- talk between protein kinases and calcineurin.

Original languageEnglish (US)
Pages (from-to)703-711
Number of pages9
JournalImmunity
Volume8
Issue number6
DOIs
StatePublished - Jun 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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