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Q. Yan, W.-B. Liu, J. Qin, J.-P. Liu, H.-G. Chen, X. Huang, L. Chen, H. Feng, Y.-M. Xiao, D. W.-C. Li; Protein Phosphatase-1 is a Major Phosphatase Responsible for Dephosphorylation of Pax-6. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4238.
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Pax-6 is an evolutionarily conserved transcription factor and acts high up in the regulatory hierarchy controlling eye and brain development and determines cell fate in the early stage of ocular cell differentiation in human, mouse, zebrafish, and Drosophila. Previous studies have shown that Pax-6 is a phospho-protein and its phosphorylation by ERK, p38 or homeodomain-interacting protein kinase 2 greatly enhances its transactivation activity. However, the protein phosphatases responsible for the dephosphorylation of Pax-6 remain unknown. Here, we present evidence to show that the protein phosphatase-1 acts as a major phosphatase to dephosphorylate Pax-6 in human lens epithelial cells.
In vitro and In vivo dephosphorylation assays, co-immunoprecipitation-linked Western blot, overexpression and RNAi of PP-1 were used to determine the dephosphorylation of Pax-6 by PP-1.
Inhibition of PP-1 with protein phosphatase inhibitor enhances hyperphosphorylation of Pax-6 (both p46 and p32). PP-1 can dephosphorylate Pax-6 in both in vitro and in vivo assays. In human lens epithelial cells, more than 90% of 46 kDa Pax-6 and 100% 32 kDa Pax-6 are found bound to the catalytic subunit of PP-1. Knockdown of PP-1 expression by RNAi substantially enhances hyperphosphorylation of Pax-6 in both forms. Mutations imitating constant dephosphorylation at the dephosphorylation sites clearly modulate the function of Pax-6.
PP-1 is a major phosphatase responsible for Pax-6 dephosphorylation in human lens epithelial cells and dephosphorylation of Pax-6 changes its function.
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