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T cell proliferation and adaptive immune responses are critically regulated by
protein phosphatase 4
#MMPMID26940341
Liao FH
; Hsiao WY
; Lin YC
; Chan YC
; Huang CY
Cell Cycle
2016[]; 15
(8
): 1073-83
PMID26940341
show ga
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 AMPK?1 retarded the
proliferation of WT T cells. Further investigations showed that PP4
co-immunoprecipitated with AMPK?1, 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.
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