April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Protein Phosphatase-1 Acts as a Major Phosphatase in the Ocular Lens and Regulates Multiple Important Targets Including P53, Pax-6 and Akt1
Author Affiliations & Notes
  • D. W. Li
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
    Ophthalmology & Visual Sciences, University of Nebraska Med Center, Omaha, Nebraska
  • L. Xiao
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
    College of Life Sciences, Hunan Normal University, Changsha, China
  • L. Gong
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
  • D. Yuan
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
  • M. Deng
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
  • L. Zhang
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
    College of Life Sciences, Hunan Normal University, Changsha, China
  • J. Liu
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
  • S. Sun
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
    College of Life Sciences, Hunan Normal University, Changsha, China
  • J. Liu
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
    College of Life Sciences, Hunan Normal University, Changsha, China
  • H. Ma
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
  • Footnotes
    Commercial Relationships  D.W. Li, None; L. Xiao, None; L. Gong, None; D. Yuan, None; M. Deng, None; L. Zhang, None; J. Liu, None; S. Sun, None; J. Liu, None; H. Ma, None.
  • Footnotes
    Support  NIH Grants EY15765 and EY18380
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2627. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: cataract • signal transduction • phosphorylation 
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