Distinct tissue and cellular distribution of two major isoforms of calcineurin

Hongsi Jiang, Fei Xiong, Suming Kong, Toshikazu Ogawa, Masakazu Kobayashi, Jun Liu

Research output: Contribution to journalArticle

Abstract

The protein phosphatase calcineurin is known to be an essential intracellular signal transducer involved in the TCR-mediated signal transduction pathway and is the common target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. The catalytic subunit of calcineurin exists in multiple isoforms, but their functional differences are not known. It has been assumed that the α isoform of calcineurin is the relevant isoform mediating TCR signaling. Recently, calcineurin α was knocked out in mice, but no defect in the TCR-mediated IL-2 production was observed, suggesting that another isoform of calcineurin mediates the TCR signal transduction pathway. We have generated specific polyclonal antibodies against the α and the β2 isoforms of calcineurin and examined their distribution in murine tissues and immune cells by immunohistochemical staining and Western blot analysis. We found that the β2 isoform of calcineurin is predominant in T and B lymphocytes as well as in thymus compared to the α isoform, suggesting that the β2 isoform may play a key role in TCR signaling. Furthermore, we observed that the two isoforms exhibit distinct expression patterns in both kidney and thymus, indicating that the two isoforms of calcineurin have distinct cellular functions. Together, these findings raise the possibility that the nephrotoxicity associated with CsA and FK506 can be reduced by designing novel inhibitors of calcineurin that target specific isoforms of the enzyme.

Original languageEnglish (US)
Pages (from-to)663-669
Number of pages7
JournalMolecular Immunology
Volume34
Issue number8-9
DOIs
StatePublished - Jun 1997
Externally publishedYes

Fingerprint

Calcineurin
Tissue Distribution
Protein Isoforms
Tacrolimus
Thymus Gland
Cyclosporine
Signal Transduction
Phosphoprotein Phosphatases
Immunosuppressive Agents
Transducers
Interleukin-2
Catalytic Domain
B-Lymphocytes
Western Blotting
Staining and Labeling
T-Lymphocytes
Kidney

Keywords

  • Antibodies
  • Calcineurin
  • Immunosuppression
  • T cell signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Distinct tissue and cellular distribution of two major isoforms of calcineurin. / Jiang, Hongsi; Xiong, Fei; Kong, Suming; Ogawa, Toshikazu; Kobayashi, Masakazu; Liu, Jun.

In: Molecular Immunology, Vol. 34, No. 8-9, 06.1997, p. 663-669.

Research output: Contribution to journalArticle

Jiang, Hongsi ; Xiong, Fei ; Kong, Suming ; Ogawa, Toshikazu ; Kobayashi, Masakazu ; Liu, Jun. / Distinct tissue and cellular distribution of two major isoforms of calcineurin. In: Molecular Immunology. 1997 ; Vol. 34, No. 8-9. pp. 663-669.
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