Format

Send to

Choose Destination
Nat Cell Biol. 2011 Feb;13(2):174-81. doi: 10.1038/ncb2158. Epub 2011 Jan 23.

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

Author information

1
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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.

PMID:
21258366
PMCID:
PMC3048027
DOI:
10.1038/ncb2158
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center