The role of tyrosine phosphorylation in the interaction of cellular tyrosine kinases with the T cell receptor ζ chain tyrosine‐based activation motif

Narin Osman, Susan Lucas, Doreen Cantrell

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Immunoglobulin receptor family tyrosine‐based activation motifs (ITAM) define a conserved signaling sequence, EX2 YX2L/IX7YX2L/I, that mediates coupling of the T cell antigen receptor (TCR) to protein tyrosine kinases (PTK). In the present study, we explored the role of phosphorylation of the two ITAM tyrosine residues in the interactions of the motif with the PTK ZAP‐70 and p59fyn. The data show that the phosphorylation of a single tyrosine within the motif enables binding of p59fyn, whereas phosphorylation of both tyrosines within the motif is required for maximal binding of the PTK ZAP‐70. Quantitative binding experiments show that nanomolar concentrations of the doubly phosphorylated ζ1‐ITAM are sufficient for ZAP‐70 recruitment, whereas micromolar levels of singly phosphorylated ITAM are necessary for p59fyn binding. ZAP‐70 binds with low efficiency to a singly phosphorylated ITAM, but shows preferential binding to the C‐terminal phosphotyrosine in the ITAM, whereas p59fyn binds selectively to the N‐terminal phosphotyrosine. The present data thus show that there is the potential for a singly phosphorylated ITAM to couple to cellular PTK. Moreover, the data suggest a mechanism for heterogeneity in signal transduction responses by the TCR, since ITAM could differentially couple the TCR to downstream signaling events depending on their phosphorylation state.

    Original languageEnglish
    Pages (from-to)2863-2869
    Number of pages7
    JournalEuropean Journal of Immunology
    Volume25
    Issue number10
    DOIs
    Publication statusPublished - Oct 1995

    Keywords

    • Protein tyrosine kinase
    • T cell receptor

    Fingerprint Dive into the research topics of 'The role of tyrosine phosphorylation in the interaction of cellular tyrosine kinases with the T cell receptor ζ chain tyrosine‐based activation motif'. Together they form a unique fingerprint.

  • Cite this