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The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.

T-cell receptor–induced phosphorylation of the ζ chain is efficiently promoted by ZAP-70 but not Syk

Steinberg, Marcos, Adjali, Oumeya, Swainson, Louise, Merida, Peggy, Bartolo, Vincenzo Di, Pelletier, Ludivine, Taylor, Naomi, Noraz, Nelly·2004·Blood
DOI 10.1182/blood-2003-12-4314
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Abstract

Engagement of the T-cell receptor (TCR) results in the activation of Lck/Fyn and ZAP-70/Syk tyrosine kinases. Lck-mediated tyrosine phosphorylation of signaling motifs (ITAMs) in the CD3-ζ subunits of the TCR is an initial step in the transduction of signaling cascades. However, ζ phosphorylation is also promoted by ZAP-70, as TCR-induced ζ phosphorylation is defective in ZAP-70–deficient T cells. We show that this defect is corrected by stable expression of ZAP-70, but not Syk, in primary and transformed T cells. Indeed, these proteins are differentially coupled to the TCR with a 5- to 10-fold higher association of ZAP-70 with ζ as compared to Syk. Low-level Syk-ζ binding is associated with significantly less Lck coupled to the TCR. Moreover, diminished coupling of Lck to ζ correlates with a poor phosphorylation of the positive regulatory tyr352 residue of Syk. Thus, recruitment of Lck into the TCR complex with subsequent ζ chain phosphorylation is promoted by ZAP-70 but not Syk. Importantly, the presence of ZAP-70 positively regulates the TCR-induced tyrosine phosphorylation of Syk. The interplay between Syk and ZAP-70 in thymocytes, certain T cells, and B-chronic lymphocytic leukemia cells, in which they are coexpressed, will therefore modulate the amplitude of antigen-mediated receptor signaling.

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Research works printed but not linked: 2

  1. Chen L, Lang H, Dicker F, et al. Demonstration that ZAP-70 directly contributes to enhanced B cell receptor signaling in chronic lymphocytic leukemia [abstract]. Blood. 2003;102: 34.
  2. Di Bartolo V, Malissen M, Dufour E, Sechet E, Malissen B, Acuto O. Tyrosine 315 determines optimal recruitment of ZAP-70 to the T-cell antigen receptor. Eur J Immunol. 2002;32: 568-575. · DOI

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Metadata

Authors
Steinberg, M., Adjali, O., Swainson, L., Merida, P., Bartolo, V. D., Pelletier, L., Taylor, N., & Noraz, N.
Affiliations
From the Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherches (UMR) 5535/Institut Fédératif de Recherche (IFR) 122, F-34293 Montpellier Cedex 5; and the Laboratory of Molecular Immunology, Institut Pasteur, 75724 Paris Cedex 15, France.
Venue
Blood
Publisher
American Society of Hematology
Published
2004-08-01
Volume
104
Issue
3
Pages
760-767
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2003-12-4314
Cited by
22
References
71
Language
en

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