Next Article in Journal
RORγt Inhibitor-SR1001 Halts Retinal Inflammation, Capillary Degeneration, and the Progression of Diabetic Retinopathy
Next Article in Special Issue
Is p38 MAPK Associated to Drugs of Abuse-Induced Abnormal Behaviors?
Previous Article in Journal
Complete Mitochondrial Genomes of Two Toxin-Accumulated Nassariids (Neogastropoda: Nassariidae: Nassarius) and Their Implication for Phylogeny
Article

The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation

1
Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
2
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3546; https://doi.org/10.3390/ijms21103546
Received: 18 April 2020 / Revised: 13 May 2020 / Accepted: 15 May 2020 / Published: 17 May 2020
(This article belongs to the Special Issue P38 Signaling Pathway)
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. View Full-Text
Keywords: arginine methylation; erythroid differentiation; MKK3; phosphorylation, PRMT1; p38 MAPK arginine methylation; erythroid differentiation; MKK3; phosphorylation, PRMT1; p38 MAPK
Show Figures

Figure 1

MDPI and ACS Style

Liu, M.-Y.; Hua, W.-K.; Chen, C.-J.; Lin, W.-J. The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation. Int. J. Mol. Sci. 2020, 21, 3546. https://doi.org/10.3390/ijms21103546

AMA Style

Liu M-Y, Hua W-K, Chen C-J, Lin W-J. The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation. International Journal of Molecular Sciences. 2020; 21(10):3546. https://doi.org/10.3390/ijms21103546

Chicago/Turabian Style

Liu, Mei-Yin, Wei-Kai Hua, Chi-Ju Chen, and Wey-Jinq Lin. 2020. "The MKK-Dependent Phosphorylation of p38α Is Augmented by Arginine Methylation on Arg49/Arg149 during Erythroid Differentiation" International Journal of Molecular Sciences 21, no. 10: 3546. https://doi.org/10.3390/ijms21103546

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop