2024-03-29T00:34:20Zhttps://dspace.library.uu.nl/oai/dareoai:dspace.library.uu.nl:1874/2022402024-02-23T15:13:12Zcom_1874_296827col_1874_296828dare
URN:NBN:NL:UI:10-1874-202240
2024-02-23T16:13:12.1Z
https://dspace.library.uu.nl/handle/1874/202240
Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization
Hofman
E.G.
aut
Bader
A.N.
aut
Voortman
J.
aut
van den Heuvel
D.J.
aut
Sigismund
S.
aut
Verkleij
A.J.
aut
Gerritsen
H.C.
aut
van Bergen en Henegouwen
P.M.P.
aut
Biomolecular Imaging
aut
Cell Biology, Neurobiology and Biophysics
aut
Soft Condensed Matter and Biophysics
aut
Sub Cell Biology
aut
Sub Molecular Biophysics
aut
Dep Biologie
aut
Sub Biomolecular Imaging
aut
text
info:eu-repo/semantics/Article
2010
en
The current activation model of the EGF receptor (EGFR) predicts that binding of EGF results in dimerization and oligomerization of the EGFR, leading to the allosteric activation of the intracellular tyrosine kinase. Little is known about the regulatory mechanism of receptor oligomerization. In this study, we have employed FRET between identical fluorophores (homo-FRET) to monitor the dimerization and oligomerization state of the EGFR before and after receptor activation. Our data show that, in the absence of ligand, ∼40% of the EGFR molecules were present as inactive dimers or predimers. The monomer/predimer ratio was not affected by deletion of the intracellular domain. Ligand binding induced the formation of receptor oligomers, which were found in both the plasma membrane and intracellular structures. Ligand-induced oligomerization required tyrosine kinase activity and nine different tyrosine kinase substrate residues. This indicates that the binding of signaling molecules to activated EGFRs results in EGFR oligomerization. Induction of EGFR predimers or pre-oligomers using the EGFR fused to the FK506-binding protein did not affect signaling but was found to enhance EGF-induced receptor internalization. Our data show that EGFR oligomerization is the result of EGFR signaling and enhances EGFR internalization
Fluorescence Resonance Energy Transfer (FRET)
Protein Assembly
Protein Phosphorylation
Receptor Endocytosis
Signal Transduction
EGF
EGF Receptor
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology Inc.
2010
0021-9258
285
50
39481
0.1074/jbc.M110.164731
1874/202240
2024-02-23T16:13:12.1Z
http://purl.org/eprint/accessRights/OpenAccess