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

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 1 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.

Pubmed ID: 9655484

Authors

  • Sun L
  • Youn HD
  • Loh C
  • Stolow M
  • He W
  • Liu JO

Journal

Immunity

Publication Data

June 23, 1998

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Calcineurin
  • Calcium
  • Down-Regulation
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Phosphoproteins
  • Protein Kinase C
  • Saccharomyces cerevisiae
  • Signal Transduction
  • T-Lymphocytes