Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediat
Author: ["Jung-Mao Hsu","Chun-Te Chen","Chao-Kai Chou","Hsu-Ping Kuo","Long-Yuan Li","Chun-Yi Lin","Hong-Jen Lee","Ying-Nai Wang","Mo Liu","Hsin-Wei Liao","Bin Shi","Chien-Chen Lai","Mark T. Bedford","Chang-Hai Tsai","Mien-Chie Hung"]
Publication: Nature Cell Biology
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Abstract
The argine methyltransferase PRMT5 methylates EGFR. This modification increases EGFR trans-autophosphorylation and attenuates ERK pathway activation. Epidermal growth factor receptor (EGFR) can undergo post-translational modifications, including phosphorylation, glycosylation and ubiquitylation, leading to diverse physiological consequences and modulation of its biological activity. There is increasing evidence that methylation may parallel other post-translational modifications in the regulation of various biological processes. It is still not known, however, whether EGFR is regulated by this post-translational event. Here, we show that EGFR Arg 1175 is methylated by an arginine methyltransferase, PRMT5. Arg 1175 methylation positively modulates EGF-induced EGFR trans-autophosphorylation at Tyr 1173, which governs ERK activation. Abolishment of Arg 1175 methylation enhances EGF-stimulated ERK activation by reducing SHP1 recruitment to EGFR, resulting in augmented cell proliferation, migration and invasion of EGFR-expressing cells. Therefore, we propose a model in which the regulatory crosstalk between PRMT5-mediated Arg 1175 methylation and EGF-induced Tyr 1173 phosphorylation attenuates EGFR-mediated ERK activation.
Cite this article
Hsu, JM., Chen, CT., Chou, CK. et al. Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol 13, 174–181 (2011). https://doi.org/10.1038/ncb2158
