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 Li

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

Fingerprint

Protein Phosphatase 1
Brain
Transcription Factors
Phosphorylation
Phosphoprotein Phosphatases
Phosphoric Monoester Hydrolases
Homeodomain Proteins
Phosphoproteins
Human Development
Zebrafish
RNA Interference
Immunoprecipitation
Protein Kinases
Transcriptional Activation
Lenses
Drosophila
Genes
Western Blotting
Epithelial Cells
RNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development. / Yan, Qin; Liu, Wen Bin; Qin, Jichao; Liu, Jinping; Chen, He Ge; Huang, Xiaoqin; Chen, Lili; Sun, Shuming; Deng, Mi; Gong, Lili; Li, Yong; Zhang, Lan; Liu, Yan; Feng, Hao; Xiao, Yamei; Liu, Yun; Li, David W.

In: Journal of Biological Chemistry, Vol. 282, No. 19, 11.05.2007, p. 13954-13965.

Research output: Contribution to journalArticle

Yan, Q, Liu, WB, Qin, J, Liu, J, Chen, HG, Huang, X, Chen, L, Sun, S, Deng, M, Gong, L, Li, Y, Zhang, L, Liu, Y, Feng, H, Xiao, Y, Liu, Y & Li, DW 2007, 'Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development', Journal of Biological Chemistry, vol. 282, no. 19, pp. 13954-13965. https://doi.org/10.1074/jbc.M611476200
Yan, Qin ; Liu, Wen Bin ; Qin, Jichao ; Liu, Jinping ; Chen, He Ge ; Huang, Xiaoqin ; Chen, Lili ; Sun, Shuming ; Deng, Mi ; Gong, Lili ; Li, Yong ; Zhang, Lan ; Liu, Yan ; Feng, Hao ; Xiao, Yamei ; Liu, Yun ; Li, David W. / Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 19. pp. 13954-13965.
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