Cutting Edge: Tyrosine-Independent Transmission of Inhibitory Signals by CTLA-4 | Zendy

Tomáš Cinek | Zendy; Ali Sadra | Zendy; John B. Imboden | Zendy

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Cutting Edge: Tyrosine-Independent Transmission of Inhibitory Signals by CTLA-4

Author(s) -

Tomáš Cinek,

Ali Sadra,

John B. Imboden

Publication year - 2000

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.164.1.5

Subject(s) - mutant , jurkat cells , tyrosine , microbiology and biotechnology , inhibitory postsynaptic potential , cytoplasm , intracellular , ctla 4 , phosphorylation , secretion , tyrosine phosphorylation , sh2 domain , chemistry , t cell , biology , biochemistry , immune system , immunology , gene , neuroscience

CTLA-4 is an important inhibitor of T cell activation. We used Jurkat cells expressing mutants of murine CTLA-4 to study the structural requirements for inhibitory signaling. We find that signals for the inhibition of IL-2 secretion are delivered efficiently by a CTLA-4 mutant in which both cytoplasmic tyrosines have been replaced by phenylalanines. A CTLA-4 mutant that lacks the carboxyl-terminal half of the intracellular domain also retains the ability to inhibit, but deletion of an additional 11 aa completely abrogates that capability. We conclude that delivery of an inhibitory signal requires the membrane-proximal region of the CTLA-4 cytoplasmic domain and does not depend upon the tyrosine phosphorylation of CTLA-4.

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