ERK2-mediated C-terminal serine phosphorylation of p300 is vital to the regulation of epidermal growth factor-induced keratin 16 gene expression

Yun Ju Chen, Ying Nai Wang, Wen Chang Chang

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

We previously reported that the epidermal growth factor (EGF) regulates the gene expression of keratin 16 by activating the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling which in turn enhances the recruitment of p300 to the keratin 16 promoter. The recruited p300 functionally cooperates with Sp1 and c-Jun to regulate the gene expression of keratin 16. This study investigated in detail the molecular events incurred upon p300 whereby EGF caused an enhanced interaction between p300 and Sp1. EGF apparently induced time- and dose-dependent phosphorylation of p300, both in vitro and in vivo, through the activation of ERK2. The six potential ERK2 phosphorylation sites, including three threonine and three serine residues as revealed by sequential analysis, were first identified in vitro. Confirmation of these six sites in vivo indicated that these three serine residues (Ser-2279, Ser-2315, and Ser-2366) on the C terminus of p300 were the major signaling targets of EGF. Furthermore, the C-terminal serine phosphorylation of p300 stimulated its histone acetyltransferase activity and enhanced its interaction with Sp1. These serine phosphorylation sites on p300 controlled the p300 recruitment to the keratin 16 promoter. When all three serine residues on p300 were replaced by alanine, EGF could no longer induce the gene expression of keratin 16. Taken together, these results strongly suggested that the ERK2-mediated C-terminal serine phosphorylation of p300 was a key event in the regulation of EGF-induced keratin 16 expression. These results also constituted the first report identifying the unique p300 phosphorylation sites induced by ERK2 in vivo.

Original languageEnglish
Pages (from-to)27215-27228
Number of pages14
JournalJournal of Biological Chemistry
Volume282
Issue number37
DOIs
Publication statusPublished - Sep 14 2007
Externally publishedYes

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Keratin-16
Phosphorylation
Epidermal Growth Factor
Gene expression
Serine
Gene Expression
Histone Acetyltransferases
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Threonine
Alanine
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

ERK2-mediated C-terminal serine phosphorylation of p300 is vital to the regulation of epidermal growth factor-induced keratin 16 gene expression. / Chen, Yun Ju; Wang, Ying Nai; Chang, Wen Chang.

In: Journal of Biological Chemistry, Vol. 282, No. 37, 14.09.2007, p. 27215-27228.

Research output: Contribution to journalArticle

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