The protein interactions of the immunoglobulin receptor family tyrosine-based activation motifs present in the T cell receptor ζ subunits and the CD3 γ,δ and ε chains

Narin Osman, Helen Turner, Susan Lucas, Karin Reif, Doreen A. Cantrell (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    83 Citations (Scopus)

    Abstract

    Immunoglobulin family tyrosine-based activation motifs (ITAM), which define the conserved signaling sequence EX2YX2L/IX7YX2L/I, couple the T cell antigen receptor (TCR) to cellular proteins including protein tyrosine kinases (PTK) and adapter molecules. The TCR is a multichain complex with four invariant chains CD3 γ, δ and ε that each contain a single ITAM and the TCR ζ chain that contains three ITAM. The present study explores the protein interactions of the doubly phosphorylated CD3 γ, δ, ε ITAM to determine whether they have common or unique biochemical properties. The data show that the doubly phosphorylated ITAM all bind the PTK ZAP-70, but the ITAM also variably bind the PTK p59fyn and the adapters Shc, Grb-2 and the p85 regulatory subunit of phosphoinositol 3' kinase. The CD3 and ζITAM display a hierarchy of ZAP-70 binding: ζ1 = γ = δ > ζ3 > ζ2 = ε. She, Grb-2 and p85 could bind the ζITAM and the CD3 γ and δ ITAM, but not the CD3 ε ITAM. There were also subtle differences in the hierarchy of reactivity of these adapters for the CD3 γ,δ and ζ ITAM that show that the ζ, CD3 γ, δ and ε ITAM have different binding properties. The present study thus shows that the different ITAM of the TCR/CD3 complex can interact with different cytosolic effecters, indicating that differential ITAM phosphorylation during T cell activation could be a mechanism to generate signaling diversity by the TCR complex.

    Original languageEnglish
    Pages (from-to)1063-1068
    Number of pages6
    JournalEuropean Journal of Immunology
    Volume26
    Issue number5
    DOIs
    Publication statusPublished - 1 May 1996

    Keywords

    • CD3
    • Immunoglobulin family tyrosine-based activation motif
    • Signaling
    • ZAP-70

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