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A sequence conserved between CD 5 and CD 6 binds an FERM domain and exerts a restraint on T‐cell activation
Author(s) -
Breuning Johannes,
Brown Marion H.
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13025
Subject(s) - radixin , moesin , ezrin , microbiology and biotechnology , biology , cytoplasm , peptide sequence , cytoskeleton , signal transducing adaptor protein , intracellular , phosphorylation , conserved sequence , biochemistry , cell , gene
Summary CD 5 and CD 6 are related surface receptors that limit and promote T‐cell responses. Co‐stimulatory effects of CD 6 depend on binding a cell surface ligand, CD 166, and recruitment of the intracellular adaptor proteins GADS and SLP ‐76 by C‐terminal phosphotyrosines. We have continued to identify interactions of CD 5 and CD 6 to understand their roles in T‐cell activation. In a screen to identify binding partners for peptides containing a cytoplasmic sequence, SDSDY conserved between CD 5 and CD 6, we identified ezrin radixin moesin ( ERM ) proteins, which link plasma membrane proteins to actin. Purified radixin FERM domain bound directly to CD 5 and CD 6 SDSDY peptides in a phosphorylation‐dependent manner ( K D = 0·5‐2 μ m ) at 37°. In human T‐cell blasts, mutation of the CD 6 SDSDY sequence enhanced CD 69 expression in response to CD 3 monoclonal antibody. In this proximal readout, interactions of the SDSDY sequence were dominant compared with the C‐terminal tyrosines of CD 6. In contrast, in a more downstream readout, interleukin‐2 expression, in response to immobilized CD 3 and CD 6 monoclonal antibodies, the C‐terminal tyrosines were dominant. The data suggest that varying functional effects of CD 6 and potentially CD 5 depend on interactions of different cytoplasmic regions with the cytoskeleton and alter depending on the stimuli.