Control of epidermal growth factor receptor endocytosis by receptor dimerization, rather than receptor kinase activation.

Abstract:

:Given that ligand binding is essential for the rapid internalization of epidermal growth factor receptor (EGFR), the events induced by ligand binding probably contribute to the regulation of EGFR internalization. These events include receptor dimerization, activation of intrinsic tyrosine kinase activity and autophosphorylation. Whereas the initial results are controversial regarding the role of EGFR kinase activity in EGFR internalization, more recent data suggest that EGFR kinase activation is essential for EGFR internalization. However, we have shown here that inhibition of EGFR kinase activation by mutation or by chemical inhibitors did not block EGF-induced EGFR internalization. Instead, proper EGFR dimerization is necessary and sufficient to stimulate EGFR internalization. We conclude that EGFR internalization is controlled by EGFR dimerization, rather than EGFR kinase activation. Our results also define a new role for EGFR dimerization: by itself it can drive EGFR internalization, independent of its role in the activation of EGFR kinase.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Wang Q,Villeneuve G,Wang Z

doi

10.1038/sj.embor.7400491

keywords:

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

942-8

issue

10

eissn

1469-221X

issn

1469-3178

pii

7400491

journal_volume

6

pub_type

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