Premium
Differential Roles of Grb 2 and AP ‐2 in p38 MAPK ‐ and EGF ‐Induced EGFR Internalization
Author(s) -
Grandal Michael V.,
Grøvdal Lene M.,
Henriksen Lasse,
Andersen Mette H.,
Holst Mikkel R.,
Madshus Inger H.,
van Deurs Bo
Publication year - 2012
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2011.01322.x
Subject(s) - internalization , endocytosis , epidermal growth factor , microbiology and biotechnology , biology , endocytic cycle , mapk/erk pathway , downregulation and upregulation , receptor , signal transduction , biochemistry , gene
The epidermal growth factor receptor ( EGFR ) is an important regulator of normal growth and differentiation, and it is involved in the pathogenesis of many cancers. Endocytic downregulation is central in terminating EGFR signaling after ligand stimulation. It has been shown that p38MAPK activation also can induce EGFR endocytosis. This endocytosis lacks many of the characteristics of ligand‐induced EGFR endocytosis. We compared the two types of endocytosis with regard to the requirements for proteins in the internalization machinery. Both types of endocytosis require clathrin, but while epidermal growth factor (EGF) ‐induced EGFR internalization also required Grb 2 , p38MAPK ‐induced internalization did not. Interestingly , AP ‐2 knock down blocked p38MAPK ‐induced EGFR internalization, but only mildly affected EGF ‐induced internalization. In line with this, simultaneously mutating two AP ‐2 interaction sites in EGFR affected p38MAPK ‐induced internalization much more than EGF ‐induced EGFR internalization. Thus, it seems that EGFR in the two situations uses different sets of internalization mechanisms.