Protein Kinase C-θ Participates in NF-κB Activation Induced by CD3-CD28 Costimulation through Selective Activation of IκB Kinase β

Lin, Xin; O’Mahony, Alison; Mu, Yajun; Geleziunas, Romas; Greene, Warner C.

doi:10.1128/mcb.20.8.2933-2940.2000

Cited by 251 publications

(238 citation statements)

References 50 publications

(60 reference statements)

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“…Protein kinase (PK)Cy, a Ca þ þ -independent PKC isoenzyme, selectively expressed in T cells, has been previously shown to play an essential role in the TCRtriggered activation of NF-kB, resulting in proliferation of mature T cells Lin et al, 2000;Sun et al, 2000). Moreover, recent observations in PKCy À/À mice suggested that PKCy is dispensable for both thymocyte differentiation and TCR-induced NF-kB activation in immature thymocytes (Sun et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

PKCθ mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia

et al. 2004

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Section: Introductionmentioning

confidence: 99%

PKCθ mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia

et al. 2004

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“…PKC is more strongly expressed in T cells than other cell types and is translocated to the site of contact between T cells and APCs, where it colocalizes with the TCR/CD3 complex in the central core of the immunological synapse after TCR/CD28 ligation (3)(4)(5)(6). Furthermore, studies using pharmocological inhibitors and PKC antisense RNA and overexpression studies using dominant negative and constitutively active mutant proteins have established a role for PKC in activation of AP-1 (7) and NF-B (8,9). PKC also synergizes with calcineurin to activate NFAT and IL-2 transcription (10,11), and with Vav to mediate IL-4 gene expression in response to CD28 costimulation (12).…”

mentioning

confidence: 99%

Differential Regulation of Th2 and Th1 Lung Inflammatory Responses by Protein Kinase Cθ

Salek-Ardakani

Halteman

et al. 2004

The Journal of Immunology

115

103

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In vitro and recent in vivo studies have identified protein kinase Cθ (PKCθ) as an important intermediate in signaling pathways leading to T cell activation, proliferation, and cytokine production. However, the importance of PKCθ to many T cell-driven inflammatory responses has not been demonstrated. In this study we show that although PKCθ is required for the development of a robust lung inflammatory response controlled by Th2 cells, it plays a lesser role in the development of a similar lung inflammatory response controlled by Th1 cells. PKCθ-deficient mice were strongly compromised in generating Th2 cells and exhibited reduced airway eosinophilia and Th2 cytokine production in lungs. PKCθ was required for the initial development of Th1 cells, with these cells exhibiting delayed kinetics of differentiation and accumulation. However, with recall Ag challenge via the airways, this defect was overcome, and lung infiltration and Th1 cytokine production were largely unimpaired in PKCθ-deficient animals. These data suggest that PKCθ can play roles in aspects of both Th2 and Th1 responses, but lung inflammation induced by Th2 cells is more dependent on this protein kinase than lung inflammation induced by Th1 cells.

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“…The T lymphocyte-restricted serine/threonine protein kinase protein kinase C (PKC ) 2 is unique among other PKC members because it colocalizes with the TCR in the T cell immunological synapse (2)(3)(4). In cultured cell lines, PKC -mediated signal transduction has been shown to result in activation of the transcription factors, AP-1 and NF-B, in response to TCR/ CD28 costimulation, ultimately culminating in the induction of expression of genes that are essential for the proliferation and function of activated T cells (5)(6)(7)(8). The physiological functions of PKC for TCR signaling were subsequently demonstrated by two independent studies with PKC -deficient mice (9,10).…”

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confidence: 99%

“…Peripheral T cells of PKC Ϫ/Ϫ mice show reduced proliferation and IL-2 production and significant impairment in AP-1 and NF-B (9, 10) as well as NFAT (10) activation in response to TCR/CD28 stimulation. Although numerous studies have implicated the I B␣ kinase IKK complex in linking PKC to NF-B activation (5)(6)(7)(8), the pathway responsible for coupling PKC to AP-1 appears to be JNK independent (9). Recently, a study has identified the stress-related STE20/ SPS1-like, proline alanine-rich kinase, SPAK, as a substrate and target of PKC in a TCR/CD28-induced signaling pathway leading to selective activation of AP-1, but not NF-B (11).…”

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confidence: 99%

Resistance to Experimental Autoimmune Encephalomyelitis and Impaired IL-17 Production in Protein Kinase Cθ-Deficient Mice

Tan

Zhao

et al. 2006

The Journal of Immunology

130

107

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The protein kinase Cθ (PKCθ) serine/threonine kinase has been implicated in signaling of T cell activation, proliferation, and cytokine production. However, the in vivo consequences of ablation of PKCθ on T cell function in inflammatory autoimmune disease have not been thoroughly examined. In this study we used PKCθ-deficient mice to investigate the potential involvement of PKCθ in the development of experimental autoimmune encephalomyelitis, a prototypic T cell-mediated autoimmune disease model of the CNS. We found that PKCθ−/− mice immunized with the myelin oligodendrocyte glycoprotein (MOG) peptide MOG35–55 were completely resistant to the development of clinical experimental autoimmune encephalomyelitis compared with wild-type control mice. Flow cytometric and histopathological analysis of the CNS revealed profound reduction of both T cell and macrophage infiltration and demyelination. Ex vivo MOG35–55 stimulation of splenic T lymphocytes from immunized PKCθ−/− mice revealed significantly reduced production of the Th1 cytokine IFN-γ as well as the T cell effector cytokine IL-17 despite comparable levels of IL-2 and IL-4 and similar cell proliferative responses. Furthermore, IL-17 expression was dramatically reduced in the CNS of PKCθ−/− mice compared with wild-type mice during the disease course. In addition, PKCθ−/− T cells failed to up-regulate LFA-1 expression in response to TCR activation, and LFA-1 expression was also significantly reduced in the spleens of MOG35–55-immunized PKCθ−/− mice as well as in in vitro-stimulated CD4+ T cells compared with wild-type mice. These results underscore the importance of PKCθ in the regulation of multiple T cell functions necessary for the development of autoimmune disease.

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Protein Kinase C-θ Participates in NF-κB Activation Induced by CD3-CD28 Costimulation through Selective Activation of IκB Kinase β

Cited by 251 publications

References 50 publications

PKCθ mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia

PKCθ mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia

Differential Regulation of Th2 and Th1 Lung Inflammatory Responses by Protein Kinase Cθ

Resistance to Experimental Autoimmune Encephalomyelitis and Impaired IL-17 Production in Protein Kinase Cθ-Deficient Mice

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