Contribution of kinases and the CD45 phosphatase to the generation of tyrosine phosphorylation patterns in the T-cell receptor complex ζ chain

Zoltán Hegedûs, Violeta Chitu, Gábor K. Tóth, Csaba Finta, Györgyi Váradi, István Andó, Éva Monostori

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The ζ subunit of the T-cell receptor complex plays a crucial role in coupling the antigen binding αβ and γδ heterodimers to the downstream activation pathways. Three tandem amino acid sequence motifs containing pairs of exactly spaced Tyr-X-X-Leu/Ile sequences, designated as Immunoreceptor Tyrosine-based Activation Motifs (ITAMs), control this function. The phosphorylated forms of ITAMs serve as docking sites for several src homology 2 (SH2) domain containing signaling proteins. The composition of the assembled signaling complex and the outcome of cell activation depends on the tyrosine phosphorylation pattern of the ζ polypeptide. The mechanism that conducts the generation of various phosphorylated forms has not yet been well established. In this study we have analyzed the ability of src family tyrosine kinases and the CD45 tyrosine phosphatase in determining the phosphorylation state of the different ITAMs and the individual tyrosine residues of the TCR ζ chain. The intracellular part of the ζ chain was phosphorylated by src family tyrosine kinases, p56(lck) and p59(fyn) in vitro. Synthetic oligopeptides representing full-length or half-sized ITAMs with a single tyrosine residue were also phosphorylated by both p56(lck) and p59(fyn). In contrast, an additional membrane proximal tyrosine residue in the human ζ chain, located outside of the ITAMs, was not phosphorylated. We also examined the activity of the CD45 phosphatase, using a panel of ITAM derivatives, in which one or both tyrosines were phosphorylated. The efficiency of ITAM dephosphorylation by CD45 was dependent on the primary sequence of the oligopeptides and the position of the phosphotyrosine residues. The in vitro data suggest that the CD45 phosphatase rather than the tyrosine kinase(s) may control the generation of specific phosphorylation patterns of the ζ chain during cell activation.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalImmunology Letters
Volume67
Issue number1
DOIs
StatePublished - Apr 1999
Externally publishedYes

Fingerprint

Immunoreceptor Tyrosine-Based Activation Motif
T-Cell Antigen Receptor
Phosphoric Monoester Hydrolases
Tyrosine
Phosphotransferases
Phosphorylation
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Oligopeptides
src-Family Kinases
Amino Acid Motifs
Phosphotyrosine
src Homology Domains
Protein-Tyrosine Kinases
Amino Acid Sequence
Antigens
Peptides
Membranes

Keywords

  • CD45
  • Fyn
  • ITAM
  • Lck
  • TCR ζ chain
  • ZAP70

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Contribution of kinases and the CD45 phosphatase to the generation of tyrosine phosphorylation patterns in the T-cell receptor complex ζ chain. / Hegedûs, Zoltán; Chitu, Violeta; Tóth, Gábor K.; Finta, Csaba; Váradi, Györgyi; Andó, István; Monostori, Éva.

In: Immunology Letters, Vol. 67, No. 1, 04.1999, p. 31-39.

Research output: Contribution to journalArticle

Hegedûs, Zoltán ; Chitu, Violeta ; Tóth, Gábor K. ; Finta, Csaba ; Váradi, Györgyi ; Andó, István ; Monostori, Éva. / Contribution of kinases and the CD45 phosphatase to the generation of tyrosine phosphorylation patterns in the T-cell receptor complex ζ chain. In: Immunology Letters. 1999 ; Vol. 67, No. 1. pp. 31-39.
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