» Articles » PMID: 7539035

Syk and ZAP-70 Mediate Recruitment of P56lck/CD4 to the Activated T Cell Receptor/CD3/zeta Complex

Overview
Journal J Exp Med
Date 1995 Jun 1
PMID 7539035
Citations 40
Authors
Affiliations
Soon will be listed here.
Abstract

During antigen recognition by T cells, CD4 and the T-cell receptor (TCR)/CD3/zeta complex are thought to interact with the same major histocompatibility complex II molecule in a stable ternary complex. Evidence has suggested that the association of CD4 with TCR/CD3/zeta requires the interaction of the protein tyrosine kinase p56lck with CD4. We have taken a biochemical approach to understand the mechanism by which p56lck and, in particular, its src homology (SH) 2 domain contributes to the association of CD4 with TCR/CD3/zeta during activation. We have previously shown that the p56lck SH2 domain binds directly to tyrosine-phosphorylated ZAP-70. Here we formally demonstrate the in vivo association of p56lck with the homologous protein tyrosine kinases Syk and ZAP-70 after CD3 stimulation of Jurkat cells. A tyrosine-phosphorylated peptide containing the sequence predicted to be optimal for binding to the SH2 domain of src family kinases specifically competes for this association, indicating that tyrosine-phosphorylated ZAP-70 and Syk bind to p56lck by an SH2-mediated interaction. We also show that the same peptide is able to compete for the activation-dependent TCR/CD4 association in Jurkat cells. Moreover, ZAP-70 and CD4 cocap only after CD3 stimulation in human T lymphoblasts. We propose that the interaction of the p56lck SH2 domain with zeta-associated tyrosine-phosphorylated ZAP-70 and/or Syk enables CD4 to associate with antigen-stimulated TCR/CD3/zeta complexes.

Citing Articles

PD-1 suppresses TCR-CD8 cooperativity during T-cell antigen recognition.

Li K, Yuan Z, Lyu J, Ahn E, Davis S, Ahmed R Nat Commun. 2021; 12(1):2746.

PMID: 33980853 PMC: 8115078. DOI: 10.1038/s41467-021-22965-9.


Galectin-9 Mediates HIV Transcription by Inducing TCR-Dependent ERK Signaling.

Colomb F, Giron L, Premeaux T, Mitchell B, Niki T, Papasavvas E Front Immunol. 2019; 10:267.

PMID: 30842775 PMC: 6391929. DOI: 10.3389/fimmu.2019.00267.


A TCR mechanotransduction signaling loop induces negative selection in the thymus.

Hong J, Ge C, Jothikumar P, Yuan Z, Liu B, Bai K Nat Immunol. 2018; 19(12):1379-1390.

PMID: 30420628 PMC: 6452639. DOI: 10.1038/s41590-018-0259-z.


Phosphorylation of a Tyrosine Residue on Zap70 by Lck and Its Subsequent Binding via an SH2 Domain May Be a Key Gatekeeper of T Cell Receptor Signaling In Vivo.

Thill P, Weiss A, Chakraborty A Mol Cell Biol. 2016; 36(18):2396-402.

PMID: 27354065 PMC: 5007795. DOI: 10.1128/MCB.00165-16.


An improved UPLC-MS/MS platform for quantitative analysis of glycerophosphoinositol in mammalian cells.

Grauso L, Mariggio S, Corda D, Fontana A, Cutignano A PLoS One. 2015; 10(4):e0123198.

PMID: 25860666 PMC: 4393254. DOI: 10.1371/journal.pone.0123198.


References
1.
Karnitz L, Sutor S, Torigoe T, Reed J, Bell M, McKean D . Effects of p56lck deficiency on the growth and cytolytic effector function of an interleukin-2-dependent cytotoxic T-cell line. Mol Cell Biol. 1992; 12(10):4521-30. PMC: 360378. DOI: 10.1128/mcb.12.10.4521-4530.1992. View

2.
Beyers A, Spruyt L, Williams A . Multimolecular associations of the T-cell antigen receptor. Trends Cell Biol. 1992; 2(9):253-5. DOI: 10.1016/0962-8924(92)90190-x. View

3.
Rudd C, Janssen O, Prasad K, Raab M, da Silva A, Telfer J . src-related protein tyrosine kinases and their surface receptors. Biochim Biophys Acta. 1993; 1155(2):239-66. DOI: 10.1016/0304-419x(93)90007-y. View

4.
June C, Fletcher M, Ledbetter J, Samelson L . Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation. J Immunol. 1990; 144(5):1591-9. View

5.
Collins T, Uniyal S, Shin J, Strominger J, Mittler R, Burakoff S . p56lck association with CD4 is required for the interaction between CD4 and the TCR/CD3 complex and for optimal antigen stimulation. J Immunol. 1992; 148(7):2159-62. View