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Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17

Author

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  • Thorsten Maretzky

    (Arthritis and Tissue Degeneration Program, Hospital for Special Surgery at Weill Medical College, Cornell University, Caspary Research Building, 535 E 70th Street, New York, New York 10021, USA.)

  • Astrid Evers

    (University Hospital Schleswig Holstein)

  • Wenhui Zhou

    (Arthritis and Tissue Degeneration Program, Hospital for Special Surgery at Weill Medical College, Cornell University, Caspary Research Building, 535 E 70th Street, New York, New York 10021, USA.)

  • Steven L. Swendeman

    (Arthritis and Tissue Degeneration Program, Hospital for Special Surgery at Weill Medical College, Cornell University, Caspary Research Building, 535 E 70th Street, New York, New York 10021, USA.)

  • Pui-Mun Wong

    (Cell Biology and Genetics Program, Weill Medical College, Cornell University)

  • Shahin Rafii

    (Cell Biology and Genetics Program, Weill Medical College, Cornell University
    Biophysics and Systems Biology, Weill Medical College, Cornell University)

  • Karina Reiss

    (University Hospital Schleswig Holstein)

  • Carl P. Blobel

    (Arthritis and Tissue Degeneration Program, Hospital for Special Surgery at Weill Medical College, Cornell University, Caspary Research Building, 535 E 70th Street, New York, New York 10021, USA.
    Cell Biology and Genetics Program, Weill Medical College, Cornell University
    Biophysics and Systems Biology, Weill Medical College, Cornell University)

Abstract

The fibroblast growth factor receptor 2-IIIb (FGFR2b) and the vascular endothelial growth factor receptor 2 (VEGFR2) are tyrosine kinases that can promote cell migration and proliferation and have important roles in embryonic development and cancer. Here we show that FGF7/FGFR2b-dependent activation of epidermal growth factor receptor (EGFR)/ERK1/2 signalling and cell migration in epithelial cells require stimulation of the membrane-anchored metalloproteinase ADAM17 and release of heparin-binding epidermal growth factor (HB-EGF). Moreover, VEGF-A/VEGFR2-induced migration of human umbilical vein endothelial cells also depends on EGFR/ERK1/2 signalling and shedding of the ADAM17 substrate HB-EGF. The pathway used by the FGF7/FGFR2b signalling axis to stimulate shedding of substrates of ADAM17, including ligands of the EGFR, involves Src, p38 mitogen-activated protein-kinase and PI3K, but does not require the cytoplasmic domain of ADAM17. Based on these findings, ADAM17 emerges as a central component in a triple membrane-spanning pathway between FGFR2b or VEGFR2 and EGFR/ERK1/2 that is required for cell migration in keratinocytes and presumably also in endothelial cells.

Suggested Citation

  • Thorsten Maretzky & Astrid Evers & Wenhui Zhou & Steven L. Swendeman & Pui-Mun Wong & Shahin Rafii & Karina Reiss & Carl P. Blobel, 2011. "Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1232
    DOI: 10.1038/ncomms1232
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