Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development

Qin Yan, Wen Bin Liu, Jichao Qin, Jinping Liu, He Ge Chen, Xiaoqin Huang, Lili Chen, Shuming Sun, Mi Deng, Lili Gong, Yong Li, Lan Zhang, Yan Liu, Hao Feng, Yamei Xiao, Yun Liu, David W.C. Li

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Pax-6 is an evolutionarily conserved transcription factor and acts high up in the regulatory hierarchy controlling eye and brain development in humans, mice, zebrafish, and Drosophila. Previous studies have shown that Pax-6 is a phosphoprotein, and its phosphorylation by ERK, p38, and 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 both in vitro and in vivo evidence to show that protein serine/threonine phosphatase-1 is a major phosphatase that directly dephosphorylates Pax-6. First, purified protein phosphatase-1 directly dephosphorylates Pax-6 in vitro. Second, immunoprecipitation-linked Western blot revealed that both protein phosphatase-1α and protein phosphatase-1β interact with Pax-6. Third, overexpression of protein phosphatase-1 in human lens epithelial cells leads to dephosphorylation of Pax-6. Finally, inhibition of protein phosphatase-1 activity by calyculin A or knockdown of protein phosphatase-1α and protein phosphatase-1β by RNA interference leads to enhanced phosphorylation of Pax-6. Moreover, our results also demonstrate that dephosphorylation of Pax-6 by protein phosphatase-1 significantly modulates its function in regulating expression of both exogenous and endogenous genes. These results demonstrate that protein phosphatase 1 acts as a major phosphatase to dephosphorylate Pax-6 and modulate its function.

Original languageEnglish (US)
Pages (from-to)13954-13965
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number19
DOIs
StatePublished - May 11 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yan, Q., Liu, W. B., Qin, J., Liu, J., Chen, H. G., Huang, X., Chen, L., Sun, S., Deng, M., Gong, L., Li, Y., Zhang, L., Liu, Y., Feng, H., Xiao, Y., Liu, Y., & Li, D. W. C. (2007). Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development. Journal of Biological Chemistry, 282(19), 13954-13965. https://doi.org/10.1074/jbc.M611476200