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The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation.
Liu, Mei-Yin; Hua, Wei-Kai; Chen, Chi-Ju; Lin, Wey-Jinq.
Afiliação
  • Liu MY; Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.
  • Hua WK; Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.
  • Chen CJ; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan.
  • Lin WJ; Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.
Int J Mol Sci ; 21(10)2020 May 17.
Article em En | MEDLINE | ID: mdl-32429593
The activation of p38 mitogen-activated protein kinases (MAPKs) through a phosphorylation cascade is the canonical mode of regulation. Here, we report a novel activation mechanism for p38α. We show that Arg49 and Arg149 of p38α are methylated by protein arginine methyltransferase 1 (PRMT1). The non-methylation mutations of Lys49/Lys149 abolish the promotive effect of p38α on erythroid differentiation. MAPK kinase 3 (MKK3) is identified as the major p38α upstream kinase and MKK3-mediated activation of the R49/149K mutant p38α is greatly reduced. This is due to a profound reduction in the interaction of p38α and MKK3. PRMT1 can enhance both the methylation level of p38α and its interaction with MKK3. However, the phosphorylation of p38α by MKK3 is not a prerequisite for methylation. MAPK-activated protein kinase 2 (MAPKAPK2) is identified as a p38α downstream effector in the PRMT1-mediated promotion of erythroid differentiation. The interaction of MAPKAPK2 with p38α is also significantly reduced in the R49/149K mutant. Together, this study unveils a novel regulatory mechanism of p38α activation via protein arginine methylation on R49/R149 by PRMT1, which impacts partner interaction and thus promotes erythroid differentiation. This study provides a new insight into the complexity of the regulation of the versatile p38α signaling and suggests new directions in intervening p38α signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arginina / Proteína-Arginina N-Metiltransferases / Proteínas Repressoras / Sistema de Sinalização das MAP Quinases / MAP Quinase Quinase 3 / Proteínas Quinases p38 Ativadas por Mitógeno / Eritropoese Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arginina / Proteína-Arginina N-Metiltransferases / Proteínas Repressoras / Sistema de Sinalização das MAP Quinases / MAP Quinase Quinase 3 / Proteínas Quinases p38 Ativadas por Mitógeno / Eritropoese Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Taiwan