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The 21- and 23-kD forms of TCRζ are generated by specific ITAM phosphorylations

Nature Immunology volume 1, pages 322–328 (2000)Cite this article

Abstract

The T cell receptor (TCR) ζ subunit contains three immunoreceptor tyrosine-based activation motifs (ITAMs) that translate effective extracellular ligand binding into intracellular signals by becoming phosphorylated into 21- and 23-kD forms. We report here that the 21-kD form of TCRζ is generated by phosphorylation of the tyrosines in the second and third ITAMs, whereas the 23-kD form is formed by the additional phosphorylation of the membrane-proximal ITAM tyrosines. The stable formation of the 21- and 23-kD species requires the binding of the tandem SH2 domains of ZAP-70. We also report that TCR-mediated signaling processes can proceed independently of either the 21- or 23-kD species of TCRζ.

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Figure 1: Generation of phosphorylated TCRζ derivatives is dependent on ZAP-70 SH2 domains.
Figure 2: Phosphorylation of all six tyrosine residues generates the 23-kD TCRζ species.
Figure 3: Specific phosphorylation of ITAM 2 and 3 yields the 21-kD TCRζ species.
Figure 4: TCR signal transduction in T cells expressing various TCRζ substitution mutants.
Figure 5: Formation of the 21-kD TCRζ requires phosphorylation of tyrosines 3–6.
Figure 6: ITAM 1 tyrosines not necessary for constitutively phosphorylated TCRζ expression.

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Acknowledgements

We thank J. Ritter for generation of mice; (dot)H. Nikaidoh and staff from the Children's Medical Center of Dallas; A. Weiss, D. Kioussis and M. Cobb for discussions; D. Kioussis for VA-CD2 transgenic constructs. This work was supported in part by a grant from the NIH (RO1 AI42953 to N. S. C. V. O.) and the Howard Hughes Medical Institute (C. A. S).

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Authors and Affiliations

  1. Center for Immunology, University of Texas Southwestern Medical Center, Dallas, 75390, TX, USA

    Nicolai S. C. van Oers & Brett Tohlen

  2. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, 75390, TX, USA

    Nicolai S. C. van Oers

  3. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, 75390, TX, USA

    Carolyn R. Moomaw, Steve Afendis & Clive A. Slaughter

  4. Centre d'Immunologie, INSERM-CNRS de Marseille-Luminy, Marseille, 13288, France

    Bernard Malissen

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  1. Nicolai S. C. van Oers
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Correspondence to Nicolai S. C. van Oers.

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van Oers, N., Tohlen, B., Malissen, B. et al. The 21- and 23-kD forms of TCRζ are generated by specific ITAM phosphorylations. Nat Immunol 1, 322–328 (2000). https://doi.org/10.1038/79774

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