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.
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
Amino Acid Sequence, Animals, Calcineurin, Calcium, Down-Regulation, Lymphocyte Activation, Mice, Molecular Sequence Data, Phosphoproteins, Protein Kinase C, Saccharomyces cerevisiae, Signal Transduction, T-Lymphocytes
Immunity
Date: Jun. 01, 1998
PubMed ID: 9655484
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