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Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation.


ABSTRACT: 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.

SUBMITTER: Hsu JM 

PROVIDER: S-EPMC3048027 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation.

Hsu Jung-Mao JM   Chen Chun-Te CT   Chou Chao-Kai CK   Kuo Hsu-Ping HP   Li Long-Yuan LY   Lin Chun-Yi CY   Lee Hong-Jen HJ   Wang Ying-Nai YN   Liu Mo M   Liao Hsin-Wei HW   Shi Bin B   Lai Chien-Chen CC   Bedford Mark T MT   Tsai Chang-Hai CH   Hung Mien-Chie MC  

Nature cell biology 20110123 2


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  ...[more]

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