scholarly journals Filamin A Phosphorylation at Serine 2152 by the Serine/Threonine Kinase Ndr2 Controls TCR-Induced LFA-1 Activation in T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Natalie Waldt ◽  
Anke Seifert ◽  
Yunus Emre Demiray ◽  
Eric Devroe ◽  
Benjamin E. Turk ◽  
...  
Keyword(s):  
T Cells ◽  
Filamin A ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals CARMA1 Is Required for Akt-Mediated NF-κB Activation in T Cells

2006 ◽  
Vol 26 (6) ◽  
pp. 2327-2336 ◽  
Author(s):  
Preeti Narayan ◽  
Brittany Holt ◽  
Richard Tosti ◽  
Lawrence P. Kane
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Functional Interaction ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Kinase C ◽  
Evolutionarily Conserved ◽  
The Common ◽  
Protein Kinase C Activation

ABSTRACT Many details of the generic pathway for induction of NF-κB have been delineated, but it is still not clear how multiple, diverse receptor systems are able to converge on this evolutionarily conserved family of transcription factors. Recent studies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for coupling the common elements of the NF-κB pathway to the T-cell receptor (TCR) and CD28. We previously demonstrated a role for the serine/threonine kinase Akt in CD28-mediated NF-κB induction. Using a CARMA1-deficient T-cell line, we have now found that the CARMA complex is required for induction of NF-κB by Akt, in cooperation with protein kinase C activation. Furthermore, using a novel selective inhibitor of Akt, we confirm that Akt plays a modulatory role in NF-κB induction by the TCR and CD28. Finally, we provide evidence for a physical and functional interaction between Akt and CARMA and for Akt-dependent phosphorylation of Bcl10. Therefore, in T cells, Akt impinges upon NF-κB signaling through at least two separate mechanisms.

scholarly journals The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1932
Author(s):  
Huixian Hong ◽  
Etty N. Benveniste
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Immune Cells ◽  
Protein Kinase Ck2 ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Kinase Ck2

Protein Kinase CK2, a constitutively active serine/threonine kinase, fulfills its functions via phosphorylating hundreds of proteins in nearly all cells. It regulates a variety of cellular signaling pathways and contributes to cell survival, proliferation and inflammation. CK2 has been implicated in the pathogenesis of hematologic and solid cancers. Recent data have documented that CK2 has unique functions in both innate and adaptive immune cells. In this article, we review aspects of CK2 biology, functions of the major innate and adaptive immune cells, and how CK2 regulates the function of immune cells. Finally, we provide perspectives on how CK2 effects in immune cells, particularly T-cells, may impact the treatment of cancers via targeting CK2.

scholarly journals A Raf-1-related p110 polypeptide associates with the CD4-p56lck complex in T cells.

1992 ◽  
Vol 12 (11) ◽  
pp. 5260-5267 ◽  
Author(s):  
K V Prasad ◽  
C E Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Receptor Complexes ◽  
T Cell Lines ◽  
The Individual

The CD4 and CD8 antigens on T cells have been shown to associate with the Src family member p56lck and a GTP-binding protein, p32. The identification of receptor interactions with intracellular mediators is essential in the elucidation of downstream signals mediated by engagement of these receptor complexes. In this study, we report the detection of an additional 110-kDa polypeptide (p110) associated with the CD4-p56lck complex in human peripheral blood T lymphocytes and leukemic T-cell lines. p110 bound preferentially to CD4-p56lck as an assembled complex and poorly, if at all, to the individual components. p110 was recognized directly by an antiserum to the C-terminal region of the serine/threonine kinase Raf-1 and is related to a p110 polypeptide detected in anti-Raf-1 immunoprecipitates. Despite its association with the CD4-p56lck complex, p110 was found to be phosphorylated predominantly on serine residues. Furthermore, phorbol ester treatment of cells resulted in a transient increase in the detection of p110 associated with CD4-p56lck, concomitant with the modulation of CD4-p56lck from the cell surface. This Raf-1-related p110 is therefore likely to play a role in signals generated from the CD4-p56lck complex. p110 may serve as a bridge between the CD4-p56lck complex and the serine/threonine kinase pathways of T-cell activation.

scholarly journals Negative Regulation of T Cell Proliferation and Interleukin 2 Production by the Serine Threonine Kinase Gsk-3

2000 ◽  
Vol 192 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Toshiaki Ohteki ◽  
Michael Parsons ◽  
Arsen Zakarian ◽  
Russell G. Jones ◽  
Linh T. Nguyen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Proliferation ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cell Responses ◽  
Specific Stimulation ◽  
Gsk 3Β

Glycogen synthase kinase (GSK)-3 is a protein serine/threonine kinase that regulates differentiation and cell fate in a variety of organisms. This study examined the role of GSK-3 in antigen-specific T cell responses. Using resting T cells from P14 T cell receptor (TCR)-transgenic mice (specific for the lymphocytic choriomeningitis virus and H-2Db), we demonstrated that GSK-3β was inactivated by serine phosphorylation after viral peptide–specific stimulation in vitro. To further investigate the role of GSK-3, we have generated a retroviral vector that expresses a constitutively active form of GSK-3β that has an alanine substitution at the regulatory amino acid, serine 9 (GSK-3βA9). Retroviral transduction of P14 TCR–transgenic bone marrow stem cells, followed by reconstitution, led to the expression of GSK-3βA9 in bone marrow chimeric mice. T cells from chimeric mice demonstrate a reduction in proliferation and interleukin (IL)-2 production. In contrast, in vitro assays done in the presence of the GSK-3 inhibitor lithium led to dramatically prolonged T cell proliferation and increased IL-2 production. Furthermore, in the presence of lithium, we show that nuclear factor of activated T cells (NF-AT)c remains in the nucleus after antigen-specific stimulation of T cells. Together, these data demonstrate that GSK-3 negatively regulates the duration of T cell responses.

A Raf-1-related p110 polypeptide associates with the CD4-p56lck complex in T cells

1992 ◽  
Vol 12 (11) ◽  
pp. 5260-5267
Author(s):  
K V Prasad ◽  
C E Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Receptor Complexes ◽  
T Cell Lines ◽  
The Individual

The CD4 and CD8 antigens on T cells have been shown to associate with the Src family member p56lck and a GTP-binding protein, p32. The identification of receptor interactions with intracellular mediators is essential in the elucidation of downstream signals mediated by engagement of these receptor complexes. In this study, we report the detection of an additional 110-kDa polypeptide (p110) associated with the CD4-p56lck complex in human peripheral blood T lymphocytes and leukemic T-cell lines. p110 bound preferentially to CD4-p56lck as an assembled complex and poorly, if at all, to the individual components. p110 was recognized directly by an antiserum to the C-terminal region of the serine/threonine kinase Raf-1 and is related to a p110 polypeptide detected in anti-Raf-1 immunoprecipitates. Despite its association with the CD4-p56lck complex, p110 was found to be phosphorylated predominantly on serine residues. Furthermore, phorbol ester treatment of cells resulted in a transient increase in the detection of p110 associated with CD4-p56lck, concomitant with the modulation of CD4-p56lck from the cell surface. This Raf-1-related p110 is therefore likely to play a role in signals generated from the CD4-p56lck complex. p110 may serve as a bridge between the CD4-p56lck complex and the serine/threonine kinase pathways of T-cell activation.

scholarly journals Mechanisms of necroptosis in T cells

2011 ◽  
Vol 208 (4) ◽  
pp. 633-641 ◽  
Author(s):  
Irene L. Ch’en ◽  
Jennifer S. Tsau ◽  
Jeffery D. Molkentin ◽  
Masaaki Komatsu ◽  
Stephen M. Hedrick
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Lymphoproliferative Disease ◽  
Cell Populations ◽  
Caspase 8 ◽  
Related Protein ◽  
Cyclophilin D ◽  
Serine Threonine Kinase ◽  
Programmed Necrosis ◽  
Threonine Kinase

Cell populations are regulated in size by at least two forms of apoptosis. More recently, necroptosis, a parallel, nonapoptotic pathway of cell death, has been described, and this pathway is invoked in the absence of caspase 8. In caspase 8–deficient T cells, necroptosis occurs as the result of antigen receptor–mediated activation. Here, through a genetic analysis, we show that necroptosis in caspase 8–deficient T cells is related neither to the programmed necrosis as defined by the requirement for mitochondrial cyclophilin D nor to autophagy as defined by the requirement for autophagy-related protein 7. Rather, survival of caspase 8–defective T cells can be completely rescued by loss of receptor-interacting serine-threonine kinase (Ripk) 3. Additionally, complementation of a T cell–specific caspase 8 deficiency with a loss of Ripk3 gives rise to lymphoproliferative disease reminiscent of lpr or gld mice. In conjunction with previous work, we conclude that necroptosis in antigen-stimulated caspase 8–deficient T cells is the result of a novel Ripk1- and Ripk3-mediated pathway of cell death.

scholarly journals Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation

2020 ◽  
Vol 5 (43) ◽  
pp. eaaz0085 ◽  
Author(s):  
Takuma Misawa ◽  
Jeffrey A. SoRelle ◽  
Jin Huk Choi ◽  
Tao Yue ◽  
Kuan-wen Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Nuclear Translocation ◽  
Immunoglobulin E ◽  
Adaptive Immune Response ◽  
Humoral Response ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Follicular Helper ◽  
Polyclonal Hypergammaglobulinemia ◽  
T Follicular Helper Cell

T follicular helper cells (TFH) participate in germinal center (GC) development and are necessary for B cell production of high-affinity, isotype-switched antibodies. In a forward genetic screen, we identified a missense mutation in Prkd2, encoding the serine/threonine kinase protein kinase D2, which caused elevated titers of immunoglobulin E (IgE) in the serum. Subsequent analysis of serum antibodies in mice with a targeted null mutation of Prkd2 demonstrated polyclonal hypergammaglobulinemia of IgE, IgG1, and IgA isotypes, which was exacerbated by the T cell–dependent humoral response to immunization. GC formation and GC B cells were increased in Prkd2−/− spleens. These effects were the result of excessive cell-autonomous TFH development caused by unrestricted Bcl6 nuclear translocation in Prkd2−/− CD4+ T cells. Prkd2 directly binds to Bcl6, and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development. In response to immunization, Bcl6 repressed Prkd2 expression in CD4+ T cells, thereby committing them to TFH development. Thus, Prkd2 and Bcl6 form a mutually inhibitory positive feedback loop that controls the stable transition from naïve CD4+ T cells to TFH during the adaptive immune response.

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