Interaction of Epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

Authors

  • Nico van Belzen,

    1. Department of Molecular Cell Biology, University of Utrecht, 3584 CH Utrecht, The Netherlands
    Current affiliation:
    1. Department of Pathology, University of Limburg, Maastricht, The Netherlands
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  • Marcel Spaargaren,

    1. Department of Molecular Cell Biology, University of Utrecht, 3584 CH Utrecht, The Netherlands
    2. Hubrecht Laboratory, Netherlands Institute of Developmental Biology, 3584 CT Utrecht, The Netherlands
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  • Arie J. Verkleij,

    1. Department of Molecular Cell Biology, University of Utrecht, 3584 CH Utrecht, The Netherlands
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  • Johannes Boonstra

    Corresponding author
    1. Department of Molecular Cell Biology, University of Utrecht, 3584 CH Utrecht, The Netherlands
    • Department of Molecular Cell Biology, University of Utrecht, 3584 CH Utrecht, The Netherlands
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Abstract

Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction, however, is still unknown. Therefore, we have studied the association of mutated EGF receptors with the cytoskeleton. Receptor deletion mutants lacking almost all intracellular amino acid residues displayed no interaction with the cytoskeleton, demonstrating that the cytoplasmic receptor domain is involved in this interaction. Further analysis revealed that receptor-cytoskeleton interaction is independent of receptor kinase activity and the C-terminal 126 amino acid residues, which include the autophosphorylation sites. Furthermore, it is shown that the high-affinity receptor subclass is not essential for association of low-affinity receptors to the cytoskeleton. EGF receptor-cytoskeleton interaction was increased, however, by treatment with sphingomyelinase, an enzyme known to induce membrane protein clustering, indicating that EGF receptor clustering may cause the association to the cytoskeleton.

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