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

Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 760-767 ◽  
Author(s):  
Marcos Steinberg ◽  
Oumeya Adjali ◽  
Louise Swainson ◽  
Peggy Merida ◽  
Vincenzo Di Bartolo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Initial Step ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Signaling Cascades ◽  
Leukemia Cells

AbstractEngagement 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.

scholarly journals Lck regulates the tyrosine phosphorylation of the T cell receptor subunits and ZAP-70 in murine thymocytes.

1996 ◽  
Vol 183 (3) ◽  
pp. 1053-1062 ◽  
Author(s):  
N S van Oers ◽  
N Killeen ◽  
A Weiss
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Cell Receptor ◽  
Protein Tyrosine Kinases ◽  
Peripheral T Cells ◽  
Tcr Signal Transduction ◽  
Deficient Mice

The Src-family and Syk/ZAP-70 family of protein tyrosine kinases (PTK) are required for T cell receptor (TCR) functions. We provide evidence that the Src-family PTK Lck is responsible for regulating the constitutive tyrosine phosphorylation of the TCR zeta subunit in murine thymocytes. Moreover, ligation of the TCR expressed on thymocytes from Lck-deficient mice largely failed to induce the phosphorylation of TCR-zeta, CD3 epsilon, or ZAP-70. In contrast, we find that the TCR-zeta subunit is weakly constitutively tyrosine phosphorylated in peripheral T cells isolated from Lck-null mice. These data suggest that Lck has a functional role in regulation of TCR signal transduction in thymocytes. In peripheral T cells, other Src-family PTKs such as Fyn may partially compensate for the absence of Lck.

scholarly journals T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells

2016 ◽  
Vol 12 (11) ◽  
pp. e1006030 ◽  
Author(s):  
Aileen G. Rowan ◽  
Aviva Witkover ◽  
Anat Melamed ◽  
Yuetsu Tanaka ◽  
Lucy B. M. Cook ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
T Cell Receptor Vβ

scholarly journals Polyubiquitin-dependent recruitment of NEMO/IKKγ into T cell receptor signaling microclusters

2019 ◽  
Author(s):  
Elizabeth A. DeRiso ◽  
Andrea L. Szymczak-Workman ◽  
Angela Montecalvo ◽  
Joanne M. Murphy ◽  
Maria-Cristina Seminario ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Adaptor Proteins ◽  
Cell Receptor ◽  
Human T Cells ◽  
T Cell Receptor Signaling ◽  
Signaling Microclusters ◽  
Cell Receptor Signaling

AbstractThe NF-κB essential modulator protein (NEMO) is required for activation of canonical NF-κB by the T cell antigen receptor (TCR). However, the subcellular localization of NEMO during this process is not well understood. By dynamically imaging fluorescent NEMO chimeras in live human T cells, we demonstrate that NEMO is rapidly recruited into TCR microclusters via domains previously implicated in the recognition of linear and K63-linked polyubiquitin. The recruitment of NEMO into TCR microclusters requires the activities of the tyrosine kinases Lck and ZAP-70, but not the adaptor proteins LAT or SLP-76. Thus, our findings reveal that the pathways leading from TCR to NF-κB bifurcate downstream of ZAP-70 to independently control the recruitment and activation of NEMO.

scholarly journals Identification, cloning, and characterization of a novel human T-cell- specific tyrosine kinase located at the hematopoietin complex on chromosome 5q

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1561-1572 ◽  
Author(s):  
S Gibson ◽  
B Leung ◽  
JA Squire ◽  
M Hill ◽  
N Arima ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
T Lymphocytes ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Phosphorylation Site ◽  
Cell Receptor ◽  
Cytokine Receptors

Signal transduction through the T-cell receptor and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Because neither the T-cell receptor nor cytokine receptors contain intrinsic kinase domains, signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. Although several members of the SRC and SYK families of tyrosine kinases have been implicated in signal transduction in lymphocytes, it seems likely that additional tyrosine kinases involved in signal transduction remain to be identified. To identify unique T-cell tyrosine kinases, we used polymerase chain reaction-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. We have cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes (EMT) and natural killer (NK) cells. The cDNA of EMT predicts an open reading frame of 1866 bp encoding a protein with a predicted size of 72 Kd, which is in keeping with its size on Western blotting. A single 6.2-kb EMT mRNA and 72-Kd protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. EMT contains both SH2 and SH3 domains, as do many other intracellular kinases. EMT does not contain the N-terminal myristylation site or the negative regulatory tyrosine phosphorylation site in its carboxyterminus that are found in the SRC family of tyrosine kinases. EMT is related to the B-cell progenitor kinase (BPK), which has recently been implicated in X-linked hypogammaglobulinemia, to the TECI mammalian kinase, which has been implicated in liver neoplasia, to the more widely expressed TECII mammalian kinase, and to the Drosophila melanogaster Dsrc28 kinase. Sequence comparison suggests that EMT is likely the human homologue of a recently identified murine interleukin-2 (IL-2)-inducible T cell kinase (ITK). However, unlike ITK, EMT message and protein levels do not vary markedly on stimulation of human IL-2-responsive T cells with IL-2. Taken together, it seems that EMT is a member of a new family of intracellular kinases that includes BPK, TECI, and TECII. EMT was localized to chromosome 5q31–32, a region that contains the genes for several growth factors and receptors as well as early activation genes, particularly those involved in the hematopoietic system. Furthermore, the 5q31–32 region is implicated in the genesis of the 5q- syndrome associated with myelodysplasia and development of leukemia.(ABSTRACT TRUNCATED AT 400 WORDS)

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