Swiprosin-1 Expression Is Up-Regulated through Protein Kinase C-θ and NF-κB Pathway in T Cells
5
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Swiprosin-1 exhibits the highest expression in CD8+ T cells and immature B cells and has been proposed to play a role in lymphocyte biology through actin remodeling. However, regulation of swiprosin-1 gene expression is poorly understood. Here we report that swiprosin-1 is up-regulated in T cells by PKC pathway. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that PKC-θ is involved in the expression of swiprosin-1 in the human T cells. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. Interestingly, swiprosin-1 expression is only reduced by treatment with NF-κB inhibitors but not by NF-AT inhibitor,suggesting that the NF-κB pathway is critical for regulation of swiprosin-1 expression. Collectively, these results suggest that swiprosin-1 is a PKC-θ-inducible gene and that it may modulate the late phase of T cell activation after antigen challenge.
Abstract
Swiprosin-1 exhibits the highest expression in CD8+ T cells and immature B cells and has been proposed to play a role in lymphocyte biology through actin remodeling. However, regulation of swiprosin-1 gene expression is poorly understood. Here we report that swiprosin-1 is up-regulated in T cells by PKC pathway. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that PKC-θ is involved in the expression of swiprosin-1 in the human T cells. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. Interestingly, swiprosin-1 expression is only reduced by treatment with NF-κB inhibitors but not by NF-AT inhibitor,suggesting that the NF-κB pathway is critical for regulation of swiprosin-1 expression. Collectively, these results suggest that swiprosin-1 is a PKC-θ-inducible gene and that it may modulate the late phase of T cell activation after antigen challenge.
참고문헌 (27)
- Vuadens, F., "Identification of swiprosin 1 in human lymphocytes", Proteomics, 4, pp.2216~2220 (2004)
- Avramidou, A., "The novel adaptor protein Swiprosin-1 enhances BCR signals and contributes to BCR-induced apoptosis", Cell Death Differ, 14, pp.1936~1947 (2007)
- T.P. Ramesh, "Swiprosin-1 Regulates Cytokine Expression of Human Mast Cell Line HMC-1 through Actin Remodeling", Immune Network, 9(6), pp.274~284 (2009), 대한면역학회
- Blagoev, B., "Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics", Nat. Biotechnol, 22, pp.1139~1145 (2004)
- Mielenz, D., "Lipid rafts associate with intracellular B cell receptors and exhibit a B cell stage-specific protein composition", J. Immunol, 174, pp.3508~3517 (2005)
- Chang-Duk Jun, "Actin Engine in Immunological Synapse", Immune Network, 12(3), pp.71~83 (2012), 대한면역학회
- Meng, X., "Compositional characterization of the cytoskeleton of NK-like cells", J. Proteome. Res, 4, pp.2081~2087 (2005)
- Thylur, R. P., "Swiprosin-1 is expressed in mast cells and up-regulated through the protein kinase C beta I", eta pathway, 2009, pp.108, 705~715
- Hayashi, K., "Protein kinase C theta (PKCtheta): a key player in T cell life and death", Pharmacol. Res, 55, pp.537~544 (2007)
- Freeley, M., "Regulating the regulator: Phosphorylation of PKC θ in T Cells", Front. Immunol, 3, pp.227~ (2012)
- Kwon, M. J., "PKC-θ is a drug target for prevention of T cell-mediated autoimmunity and allograft rejection", Endocr. Metab. Immune Disord. Drug Targets, 10, pp.367~372 (2010)
- Manicassamy, S, "A critical role for protein kinase C-theta-mediated T cell survival in cardiac allograft rejection", J. Immunol, 181, pp.513~520 (2008)
- Murphy, K. M., "The lineage decisions of helper T cells", Nat. Rev. Immunol, 2, pp.933~944 (2002)
- Shahabi, N. A., "Stromal cell-derived factor 1-alpha (SDF)-induced human T cell chemotaxis becomes phosphoinositide 3-kinase (PI3K)-independent: role of PKC-theta", J. Leukoc. Biol, 83, pp.663~671 (2008)
- Tan, S. L., "Emerging and diverse roles of protein kinase C in immune cell signalling", Biochem. J, 376, pp.545~552 (2003)
- Michalczyk, I., "The emerging role of protein kinase Cθ in cytoskeletal signaling", J. Leukoc. Biol, 93, pp.319~327 (2013)
- Manicassamy, S., "Protein kinase C-theta-mediated signals enhance CD4＋ T cell survival by up-regulating Bcl-xL", J. Immunol, 176, pp.6709~6716 (2006)
- Isakov, N., "Protein kinase C(theta) in T cell activation", Annu. Rev. Immunol, 20, pp.761~794 (2002)
- Altman, A., "Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death", J. Biochem, 132, pp.841~846 (2002)
- Boschelli, D. H., "Small molecule inhibitors of PKCTheta as potential antiinflammatory therapeutics", Curr. Top. Med. Chem, 9, pp.640~654 (2009)
- Lanzavecchia, A., "Understanding the mechanisms of sustained signaling and T cell activation", J. Exp. Med, 185, pp.1717~1719 (1997)
- Gardner, P, "Calcium and T lymphocyte activation", Cell, 59, pp.15~20 (1989)
- Rao, A., "Transcription factors of the NFAT family: regulation and function", Annu. Rev. Immunol, 15, pp.707~747 (1997)
- Chan, A. C., "The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction", Annu. Rev. Immunol, 12, pp.555~592 (1994)
- Bootman, M. D., "The elemental principles of calcium signaling", Cell, 83, pp.675~678 (1995)
- Vega, I. E., "A novel calcium-binding protein is associated with tau proteins in tauopathy", J. Neurochem, 106, pp.96~106 (2008)
- Dütting, S., "Fraternal twins: Swiprosin-1", EFhd2 and Swiprosin-2, Cell Commun. Signal, pp.2011, 9[DOI]