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.
Sun
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Center for Cancer Research and Deparmtent of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Youn
H D
HD
Loh
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Stolow
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He
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Liu
J O
JO
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D019703:Calcineurin / Q000276:immunology*; D002118:Calcium / Q000276:immunology; D015536:Down-Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000276:immunology*; D011493:Protein Kinase C / Q000276:immunology; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; C113151:Cabin1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011493:Protein Kinase C; D019703:Calcineurin; D002118:Calcium