| First Author | Liao FH | Year | 2016 |
| Journal | Cell Cycle | Volume | 15 |
| Issue | 8 | Pages | 1073-83 |
| PubMed ID | 26940341 | Mgi Jnum | J:309527 |
| Mgi Id | MGI:6758330 | Doi | 10.1080/15384101.2016.1156267 |
| Citation | Liao FH, et al. (2016) T cell proliferation and adaptive immune responses are critically regulated by protein phosphatase 4. Cell Cycle 15(8):1073-83 |
| abstractText | 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. |
