Functional cleavage of the common cytokine receptor gamma chain (gammac) by calpain.

The small subunit of calpain, a calcium-dependent cysteine protease, was found to interact with the cytoplasmic domain of the common cytokine receptor gamma chain (gammac) in a yeast two-hybrid interaction trap assay. This interaction was functional as demonstrated by the ability of calpain to cleave in vitro-translated wild-type gammac, but ...
not gammac containing a mutation in the PEST (proline, glutamate, serine, and threonine) sequence in its cytoplasmic domain, as well as by the ability of endogenous calpain to mediate cleavage of gammac in a calcium-dependent fashion. In T cell receptor-stimulated murine thymocytes, calpain inhibitors decreased cleavage of gammac. Moreover, in single positive CD4(+) thymocytes, not only did a calpain inhibitor augment CD3-induced proliferation, but antibodies to gammac blocked this effect. Finally, treatment of cells with ionomycin could inhibit interleukin 2-induced STAT protein activation, but this inhibition could be reversed by calpain inhibitors. Together, these data suggest that calpain-mediated cleavage of gammac represents a mechanism by which gammac-dependent signaling can be controlled.
Mesh Terms:
Amino Acid Sequence, Amino Acid Substitution, Animals, Base Sequence, CD4-Positive T-Lymphocytes, Calpain, Cells, Cultured, DNA Primers, Glutamic Acid, Humans, Interleukin-2, Ionomycin, Lymphocyte Activation, Macromolecular Substances, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mutagenesis, Site-Directed, Polymerase Chain Reaction, Proline, Protein Biosynthesis, Receptor-CD3 Complex, Antigen, T-Cell, Receptors, Cytokine, Recombinant Proteins, Sequence Alignment, Serine, Signal Transduction, Substrate Specificity, T-Lymphocytes, Threonine
Proc. Natl. Acad. Sci. U.S.A.
Date: Oct. 14, 1997
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