Syk and ZAP-70 Mediate Recruitment of P56lck/CD4 to the Activated T Cell Receptor/CD3/zeta Complex
Overview
General Medicine
Authors
Affiliations
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.
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.
Thill P, Weiss A, Chakraborty A Mol Cell Biol. 2016; 36(18):2396-402.
PMID: 27354065 PMC: 5007795. DOI: 10.1128/MCB.00165-16.
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.