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Spatial control of EGF receptor activation by reversible dimerization on living cells

Author

Listed:
  • Inhee Chung

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

  • Robert Akita

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

  • Richard Vandlen

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

  • Derek Toomre

    (Department of Cell Biology,)

  • Joseph Schlessinger

    (Deparment of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, USA)

  • Ira Mellman

    (Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA)

Abstract

A time and a place for EGFR Here, the dimerization dynamics of individual epidermal growth factor receptor (EGFR) molecules have been determined in living cells in real time using a quantum-dot-based approach. Signalling by EGFR, a type I receptor kinase that has been implicated in a number if human carcinomas, is preceded by receptor dimerization. It has been widely assumed that ligand binding is required to trigger conformation changes in EGFR, which in turn lead to dimer formation and kinase activation. However, this new work shows that dimerization is a continuous and reversible process, with ligand binding serving to stabilize receptor dimers by decreasing their rate of dissociation, thereby increasing the stable dimer population in a given cell. In addition, the location of the receptor is important, with spontaneous dimer formation being more prevalent at the cell margins than at the cell centre.

Suggested Citation

  • Inhee Chung & Robert Akita & Richard Vandlen & Derek Toomre & Joseph Schlessinger & Ira Mellman, 2010. "Spatial control of EGF receptor activation by reversible dimerization on living cells," Nature, Nature, vol. 464(7289), pages 783-787, April.
    • Handle: RePEc:nat:nature:v:464:y:2010:i:7289:d:10.1038_nature08827
    DOI: 10.1038/nature08827
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    Cited by:

    1. Michael G. Sugiyama & Aidan I. Brown & Jesus Vega-Lugo & Jazlyn P. Borges & Andrew M. Scott & Khuloud Jaqaman & Gregory D. Fairn & Costin N. Antonescu, 2023. "Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Shwetha Srinivasan & Raju Regmi & Xingcheng Lin & Courtney A. Dreyer & Xuyan Chen & Steven D. Quinn & Wei He & Matthew A. Coleman & Kermit L. Carraway & Bin Zhang & Gabriela S. Schlau-Cohen, 2022. "Ligand-induced transmembrane conformational coupling in monomeric EGFR," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Yunqing Li & Serena M. Arghittu & Marina S. Dietz & Gabriel J. Hella & Daniel Haße & Davide M. Ferraris & Petra Freund & Hans-Dieter Barth & Luisa Iamele & Hugo Jonge & Hartmut H. Niemann & Roberto Co, 2024. "Single-molecule imaging and molecular dynamics simulations reveal early activation of the MET receptor in cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Miroslav Blumenberg, 2014. "Differential Transcriptional Effects of EGFR Inhibitors," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-14, September.
    5. Zhdanov, Vladimir P., 2015. "Control of tissue growth by locally produced activator: Liver regeneration," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 421(C), pages 279-285.
    6. Hui Deng & Qian Lei & Chengdi Wang & Zhoufeng Wang & Hai Chen & Gang Wang & Na Yang & Dan Huang & Quanwei Yu & Mengling Yao & Xue Xiao & Guonian Zhu & Cheng Cheng & Yangqian Li & Feng Li & Panwen Tian, 2022. "A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    7. Manas Pratim Chakraborty & Diptatanu Das & Purav Mondal & Pragya Kaul & Soumi Bhattacharyya & Prosad Kumar Das & Rahul Das, 2024. "Molecular basis of VEGFR1 autoinhibition at the plasma membrane," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Ziya Kalay & Takahiro K Fujiwara & Akihiro Kusumi, 2012. "Confining Domains Lead to Reaction Bursts: Reaction Kinetics in the Plasma Membrane," PLOS ONE, Public Library of Science, vol. 7(3), pages 1-8, March.

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