國家衛生研究院 NHRI:Item 3990099045/9608
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    题名: T cell proliferation and adaptive immune responses are critically regulated by protein phosphatase 4
    作者: Liao, FH;Hsiao, WY;Lin, YC;Chan, YC;Huang, CY
    贡献者: Immunology Research Center
    摘要: The clonal expansion of activated T cells is pivotal for the induction of protective immunity. Protein phosphatase 4 (PP4) is a ubiquitously expressed serine/threonine phosphatase with reported functions in thymocyte development and DNA damage responses. However, the role of PP4 in T cell immunity has not been thoroughly investigated. In this report, our data showed that T cell-specific ablation of PP4 resulted in defective adaptive immunity, impaired T cell homeostatic expansion, and inefficient T cell proliferation. This hypo-proliferation was associated with a partial G1-S cell cycle arrest, enhanced transcriptions of CDK inhibitors and elevated activation of AMPK. In addition, resveratrol, a known AMPK activator, induced similar G1-S arrests, while lentivirally-transduced WT or constitutively-active AMPKalpha1 retarded the proliferation of WT T cells. Further investigations showed that PP4 co-immunoprecipitated with AMPKalpha1, and the over-expression of PP4 inhibited AMPK phosphorylation, thereby implicating PP4 for the negative regulation of AMPK. In summary, our results indicate that PP4 is an essential modulator for T cell proliferation and immune responses; they further suggest a potential link between PP4 functions, AMPK activation and G1-S arrest in activated T cells.
    日期: 2016-04
    關聯: Cell Cycle. 2016 Apr;15(8):1073-1083.
    Link to: http://dx.doi.org/10.1080/15384101.2016.1156267
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1538-4101&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000374997400012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84964477816
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