Protein kinase Cθ: the pleiotropic T-cell signalling intermediate

2014 ◽  
Vol 42 (6) ◽  
pp. 1512-1518 ◽  
Author(s):  
Katarzyna Wachowicz ◽  
Gottfried Baier
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
T Cell Activation ◽  
Th17 Cell ◽  
Cell Activation ◽  
Cell Signalling ◽  
Cell Receptor ◽  
Cell Phenotype ◽  
Inhibitory Circuits ◽  
T Cell Signalling

Activating as well as inhibitory circuits tightly regulate T-cell activation thresholds and effector differentiation processes enabling proper immune response outcomes. Recently, an additional molecular link between T-cell receptor signalling and CD4+ Th17 cell skewing has been reported, namely that protein kinase C (PKC) θ critically regulates Th17/Th1 phenotypic differentiation and plasticity in CD4+ T-cells by selectively acting as a ‘reprogramming element’ that suppresses Th1-typical genes during Th17-mediated immune activation in order to stabilize a Th17 cell phenotype.

scholarly journals Ca2+/Calmodulin-Dependent Protein Kinase II Is a Modulator of CARMA1-Mediated NF-κB Activation

2006 ◽  
Vol 26 (14) ◽  
pp. 5497-5508 ◽  
Author(s):  
Kazuhiro Ishiguro ◽  
Todd Green ◽  
Joseph Rapley ◽  
Heather Wachtel ◽  
Cosmas Giallourakis ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Dependent Protein Kinase ◽  
Immune Synapse ◽  
Protein Kinase Ii ◽  
Dependent Protein

ABSTRACT CARMA1 is a central regulator of NF-κB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-κB signaling downstream of the T-cell receptor (TCR). Computational analysis of expression neighborhoods of CARMA1-Bcl10MALT 1 for enrichment in kinases identified calmodulin-dependent protein kinase II (CaMKII) as an important component of this pathway. Here we report that Ca2+/CaMKII is redistributed to the immune synapse following T-cell activation and that CaMKII is critical for NF-κB activation induced by TCR stimulation. Furthermore, CaMKII enhances CARMA1-induced NF-κB activation. Moreover, we have shown that CaMKII phosphorylates CARMA1 on Ser109 and that the phosphorylation facilitates the interaction between CARMA1 and Bcl10. These results provide a novel function for CaMKII in TCR signaling and CARMA1-induced NF-κB activation.

scholarly journals Submicromolar La3+ concentrations block the calcium release-activated channel, and impair CD69 and CD25 expression in CD3- or thapsigargin-activated Jurkat cells

1996 ◽  
Vol 313 (3) ◽  
pp. 909-913 ◽  
Author(s):  
Claude AUSSEL ◽  
Rachid MARHABA ◽  
Claudette PELASSY ◽  
Jean-Philippe BREITTMAYER
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Calcium Release ◽  
Cell Signalling ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
T Cell Signalling ◽  
A Chain ◽  
20 Nm

The calcium release-activated channel (CRAC) opened in Jurkat cells activated either with CD3 monoclonal antibody or the endoplasmic reticulum Ca2+-ATPase blocker, thapsigargin, is blocked by La3+ with an IC50 of 20 nM. Similarly, the entry of Mn2+, used as a surrogate for Ca2+, is also blocked by submicromolar La3+ concentrations. La3+ seems to play its role simply by plugging the CRAC because this ion does not penetrate the cells, as demonstrated by chelation experiments with EGTA. Blocking the Ca2+ influx in activated Jurkat cells results in a lack of expression of CD25, a chain of the interleukin-2 receptor and of CD69, a marker of T-cell activation. By contrast, the very early steps of the T-cell signalling pathway such as the release of Ca2+ from intracellular stores and the subsequent inhibition of phosphatidylserine synthesis are not affected by La3+.

scholarly journals Activation of the Cooh-Terminal Src Kinase (Csk) by Camp-Dependent Protein Kinase Inhibits Signaling through the T Cell Receptor

2001 ◽  
Vol 193 (4) ◽  
pp. 497-508 ◽  
Author(s):  
Torkel Vang ◽  
Knut Martin Torgersen ◽  
Vibeke Sundvold ◽  
Manju Saxena ◽  
Finn Olav Levy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protein Kinase ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Type I ◽  
Dependent Protein Kinase ◽  
Dependent Protein

In T cells, cAMP-dependent protein kinase (PKA) type I colocalizes with the T cell receptor–CD3 complex (TCR/CD3) and inhibits T cell function via a previously unknown proximal target. Here we examine the mechanism for this PKA-mediated immunomodulation. cAMP treatment of Jurkat and normal T cells reduces Lck-mediated tyrosine phosphorylation of the TCR/CD3 ζ chain after T cell activation, and decreases Lck activity. Phosphorylation of residue Y505 in Lck by COOH-terminal Src kinase (Csk), which negatively regulates Lck, is essential for the inhibitory effect of cAMP on ζ chain phosphorylation. PKA phosphorylates Csk at S364 in vitro and in vivo leading to a two- to fourfold increase in Csk activity that is necessary for cAMP-mediated inhibition of TCR-induced interleukin 2 secretion. Both PKA type I and Csk are targeted to lipid rafts where proximal T cell activation occurs, and phosphorylation of raft-associated Lck by Csk is increased in cells treated with forskolin. We propose a mechanism whereby PKA through activation of Csk intersects signaling by Src kinases and inhibits T cell activation.

scholarly journals Association of tyrosine protein kinase Zap-70 with the protooncogene product p120c-cbl in T lymphocytes.

1996 ◽  
Vol 183 (1) ◽  
pp. 301-306 ◽  
Author(s):  
M Fournel ◽  
D Davidson ◽  
R Weil ◽  
A Veillette
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
Tyrosine Protein Kinase

Accumulating data show that the tyrosine protein kinase Zap-70 plays an essential role in T cell receptor-mediated signal transduction. However, the model of action, as well as the physiologically relevant substrates of Zap-70, have not been determined. We have attempted to identify a 120-kD tyrosine-phosphorylated protein (p120) that associates with Zap-70 in activated T lymphocytes. The results of our analyses showed that p120 is largely encoded by the c-cbl protooncogene. Furthermore, the association of Zap-70 with c-Cbl was shown to be induced by T cell receptor stimulation, implying that it required posttranslational modification of one or both of these products. FynT, but not Lck, also associated with c-Cbl in activated T cells. Finally, using a heterologous system, it was demonstrated that the ability of Zap-70 to cause tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated signals. As c-Cbl can associate with several other signaling molecules, it may couple Zap-70 to downstream effectors during T cell activation.

scholarly journals Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn.

1992 ◽  
Vol 175 (6) ◽  
pp. 1483-1492 ◽  
Author(s):  
D Davidson ◽  
L M Chow ◽  
M Fournel ◽  
A Veillette
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Kinase Domain ◽  
Tyrosine Protein Kinase

Recent observations suggest that the src-related tyrosine protein kinase p59fyn may be involved in antigen-induced T lymphocyte activation. As a result of alternative splicing, p59fyn exists as two isoforms that differ exclusively within a short sequence spanning the end of the Src Homology 2 (SH2) region and the beginning of the tyrosine protein kinase domain. While one p59fyn isoform (fynB) is highly expressed in brain, the alternative product (fynT) is principally found in T lymphocytes. To further understand the role of p59fyn in T cell activation and to test the hypothesis that p59fynT serves a tissue-specific function in T lymphocytes, we have examined the effects of expression of activated versions (tyrosine 528 to phenylalanine 528 mutants) of either form of p59fyn on the physiology of an antigen-specific mouse T cell hybridoma. Our results demonstrated that the two forms of fyn, expressed in equivalent amounts, efficiently enhanced antibody-induced T cell receptor (TCR)-mediated signals. In contrast, only p59fynT increased interleukin 2 production in response to antigen stimulation. This finding implies that the distinct p59fyn isoform expressed in T lymphocytes regulates the coupling of TCR stimulation by antigen/major histocompatibility complex to lymphokine production.

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