Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization
Articolo
Data di Pubblicazione:
2010
Citazione:
Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization / E.G. Hofman, A.N. Bader, J. Voortman, D.J. Van Den Heuvel, S. Sigismund, A.J. Verkleij, H.C. Gerritsen, P.M.P. Van Bergen en Henegouwen. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 285:50(2010 Dec 10), pp. 39481-39489. [10.1074/jbc.M110.164731]
Abstract:
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 preoligomers 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
animals; anisotropy; cell line, tumor; epidermal growth factor; fluorescence resonance energy transfer; humans; kinetics; ligands; mice; NIH 3T3 cells; protein binding; protein-tyrosine kinases; receptor, epidermal growth factor; signal transduction; spectrometry, fluorescence; biochemistry; cell biology; molecular biology
Elenco autori:
E.G. Hofman, A.N. Bader, J. Voortman, D.J. Van Den Heuvel, S. Sigismund, A.J. Verkleij, H.C. Gerritsen, P.M.P. Van Bergen en Henegouwen
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