title: SEC2-induced superantigen and antitumor activity is regulated through calcineurin.
abstract: Once the TCR-SAg-MHC II ternary complex is established, it triggers a variety of intracellular signal transduction pathways, which provoke extreme responses in the immune system. However, the signaling events that involved in SAg-induced immune activation are not well understood. In this study, we demonstrated that the Ca(2+)/calcineurin (CaN)/nuclear factor of activated T cells (NFAT) signaling pathway was involved in SEC2-induced immune activation, and selective blockade of CaN by its inhibitor cyclosporine A (CsA) can completely inhibited the SEC2-induced T-cell stimulating potency. In addition, we selected an engineered SEC2 mutant named SAM-1 based on a series of biological activity tests, and our further studies on it not only confirmed that the CaN activity and gene transcription of its key substrates were proportional to the SEC2/SAM-1-induced T-cell stimulating potency, but also suggested that intensified Ca(2+)/CaN/NFAT signaling transduction induced by SAM-1 resulted in enhanced T-cell stimulating potency, production of cytokines and cytotoxicity, which finally elicit the improved antitumor activity of SAM-1 in vivo.
authors: Institute of Applied of Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis, P.O. Box 417, 110016, Shenyang, Liaoning, People's Republic of China.
authors: Yanli
authors: Y
authors: Liu
authors: Mingkai
authors: M
authors: Xu
authors: Huiwen
authors: H
authors: Zhang
authors: Xu
authors: X
authors: Li
authors: Zhencheng
authors: Z
authors: Su
authors: Chenggang
authors: C
authors: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism*; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D004768:Enterotoxins; D018089:Superantigens; C034959:enterotoxin C, staphylococcal; D019703:Calcineurin