Spatial activation of ezrin by epidermal growth factor receptor and focal adhesion kinase co-ordinates epithelial cell migration.

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  • Author(s): Chan GK;Chan GK; McGrath JA; McGrath JA; Parsons M; Parsons M
  • Source:
    Open biology [Open Biol] 2021 Aug; Vol. 11 (8), pp. 210166. Date of Electronic Publication: 2021 Aug 11.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Royal Society Pub Country of Publication: England NLM ID: 101580419 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2046-2441 (Electronic) Linking ISSN: 20462441 NLM ISO Abbreviation: Open Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Royal Society Pub., [2011]-
    • Subject Terms:
      Cell Movement*; Cytoskeletal Proteins/*metabolism ; Epithelial Cells/*physiology ; Focal Adhesion Protein-Tyrosine Kinases/*metabolism ; Focal Adhesions/*physiology ; Keratinocytes/*physiology; Cell Adhesion ; Cytoskeletal Proteins/genetics ; Cytoskeleton ; Epithelial Cells/cytology ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Focal Adhesion Protein-Tyrosine Kinases/genetics ; HEK293 Cells ; Humans ; Keratinocytes/cytology ; Phosphorylation ; Signal Transduction
    • Abstract:
      Epidermal growth factor receptor (EGFR) plays a critical role in the promotion of epithelial cell proliferation and migration. Previous studies have suggested a cooperative role between EGFR and integrin signalling pathways that enable efficient adhesion and migration but the mechanisms controlling this remain poorly defined. Here, we show that EGFR forms a complex with focal adhesion kinase in epithelial cells. Surprisingly, this complex enhances local Src activity at focal adhesions to promote phosphorylation of the cytoskeletal adaptor protein ezrin at Y478, leading to actomyosin contractility, suppression of focal adhesion dynamics and slower migration. We further demonstrate this regulation of Src is due to the suppression of PTP1B activity. Our data provide new insight into EGF-independent cooperation between EGFR and integrins and suggest transient interactions between these kinases at the leading edge of cells act to spatially control signalling to permit efficient motility.
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    • Contributed Indexing:
      Keywords: EGFR; FAK; epithelial cell; ezrin; focal adhesion
    • Accession Number:
      0 (Cytoskeletal Proteins)
      0 (ezrin)
      EC 2.7.10.1 (EGFR protein, human)
      EC 2.7.10.1 (ErbB Receptors)
      EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
    • Publication Date:
      Date Created: 20210810 Date Completed: 20220307 Latest Revision: 20220307
    • Publication Date:
      20240829
    • Accession Number:
      PMC8354753
    • Accession Number:
      10.1098/rsob.210166
    • Accession Number:
      34375550