The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation
| Autor: | Wei Kai Hua, Mei Yin Liu, Wey Jinq Lin, Chi Ju Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Protein-Arginine N-Methyltransferases MAP Kinase Kinase 3 Mitogen-activated protein kinase kinase p38 Mitogen-Activated Protein Kinases Mass Spectrometry Phosphorylation cascade lcsh:Chemistry 0302 clinical medicine Erythropoiesis Phosphorylation lcsh:QH301-705.5 Spectroscopy erythroid differentiation Kinase Chemistry MAPKAPK2 General Medicine Methylation Recombinant Proteins Computer Science Applications Cell biology 030220 oncology & carcinogenesis Gene Knockdown Techniques Protein Binding MAP Kinase Signaling System p38 mitogen-activated protein kinases p38 MAPK Arginine Catalysis Article Inorganic Chemistry 03 medical and health sciences Cell Line Tumor Humans MKK3 Physical and Theoretical Chemistry Protein kinase A Molecular Biology Organic Chemistry arginine methylation Enzyme Activation Repressor Proteins 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Mutation phosphorylation PRMT1 Protein Processing Post-Translational |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 10 International Journal of Molecular Sciences, Vol 21, Iss 3546, p 3546 (2020) |
| ISSN: | 1422-0067 |
| Popis: | 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 p38&alpha We show that Arg49 and Arg149 of p38&alpha are methylated by protein arginine methyltransferase 1 (PRMT1). The non-methylation mutations of Lys49/Lys149 abolish the promotive effect of p38&alpha on erythroid differentiation. MAPK kinase 3 (MKK3) is identified as the major p38&alpha upstream kinase and MKK3-mediated activation of the R49/149K mutant p38&alpha is greatly reduced. This is due to a profound reduction in the interaction of p38&alpha and MKK3. PRMT1 can enhance both the methylation level of p38&alpha and its interaction with MKK3. However, the phosphorylation of p38&alpha by MKK3 is not a prerequisite for methylation. MAPK-activated protein kinase 2 (MAPKAPK2) is identified as a p38&alpha downstream effector in the PRMT1-mediated promotion of erythroid differentiation. The interaction of MAPKAPK2 with p38&alpha is also significantly reduced in the R49/149K mutant. Together, this study unveils a novel regulatory mechanism of p38&alpha 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 p38&alpha signaling and suggests new directions in intervening p38&alpha signaling. |
| Databáze: | OpenAIRE |
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