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D. W. Li, L. Xiao, L. Gong, D. Yuan, M. Deng, L. Zhang, J. Liu, S. Sun, J. Liu, H. Ma; Protein Phosphatase-1 Acts as a Major Phosphatase in the Ocular Lens and Regulates Multiple Important Targets Including P53, Pax-6 and Akt1. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2627.
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Protein serine/threonine phosphatase-1(PP-1) is a key phosphatase in the ocular lens and regulates development, differentiation and pathogenesis. We have recently demonstrated that PP-1 plays an important role in regulating the functions of the tumor suppressor, p53, and the eye development regulator, Pax-6. In the present study, we present evidence to show that PP-1 is the major phosphatase regulating AKT signaling pathway.
Dephosphorylation assay was used to identify possible phosphatase. Co-immunoprecipitation and immunocytochemistry were used to determine the interaction between PP-1 and AKT. ShRNA and overexpression were used to knockdown or overexpress PP-1/PP2A. Cell flow cytometry was used for apoptosis assay. Western blot analysis was used to explore gene expression.
Purified PP-1 directly dephosphorylates AKT in vitro. PP-1 can directly interact with AKT in both FHL124 and ARPE-19. Stable knockdown of PP-1α or PP-1β by shRNA leads to enhanced phosphorylation of AKT at Thr-450. Overexpression of PP-1α or PP-1β results in attenuated phosphorylation of AKT at Thr-450. Moreover, our results also demonstrate that PP-1 significantly modulates AKT functions in regulating expression of the downstream genes coding for NF-ΚB, GSK-3β, α- and β-crystallins, and N-cadherin, promoting cell survival and modulating differentiation.
Our results demonstrate that PP-1 acts as a major phosphatase to dephosphorylate AKT at Thr-450 and thus modulate functions of AKT signaling pathway. In addition, PP-1 is a major phosphatase in the ocular lens and regulates functions of multiple targets including p53, Pax-6 and AKT.
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