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

Thorsten Maretzky; Astrid Evers; Wenhui Zhou; Steven L Swendeman; Pui-Mun Wong; Shahin Rafii; Karina Reiss; Carl P Blobel

doi:10.1038/ncomms1232

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

Journal article

Open access

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

Thorsten Maretzky, Astrid Evers, Wenhui Zhou, Steven L Swendeman, Pui-Mun Wong, Shahin Rafii, Karina Reiss and Carl P Blobel

Nature communications, Vol.2(1), pp.229-229

2011

DOI: 10.1038/ncomms1232

PMCID: PMC3074487

PMID: 21407195

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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.

ADAM17 Protein

Receptor, Epidermal Growth Factor - genetics

Phosphorylation

Cell Proliferation

Receptor, Fibroblast Growth Factor, Type 2 - metabolism

Humans

Transcriptional Activation

Phosphatidylinositol 3-Kinases - metabolism

Vascular Endothelial Growth Factor Receptor-2 - genetics

Intercellular Signaling Peptides and Proteins - metabolism

Fibroblast Growth Factor 7 - metabolism

Receptor, Epidermal Growth Factor - metabolism

Transfection

Mitogen-Activated Protein Kinase 1 - genetics

src-Family Kinases - metabolism

Female

Fetus

p38 Mitogen-Activated Protein Kinases - metabolism

Endothelial Cells - physiology

Cell Line

Gene Expression

Mitogen-Activated Protein Kinase 3 - genetics

Signal Transduction

Epidermal Growth Factor - genetics

Intercellular Signaling Peptides and Proteins - genetics

Vascular Endothelial Growth Factor Receptor-2 - metabolism

p38 Mitogen-Activated Protein Kinases - genetics

Epidermal Growth Factor - metabolism

Mice, Transgenic

Keratinocytes - cytology

Fibroblast Growth Factor 7 - genetics

Phosphatidylinositol 3-Kinases - genetics

Heparin-binding EGF-like Growth Factor

ADAM Proteins - metabolism

Animals

Mitogen-Activated Protein Kinase 3 - metabolism

Endothelial Cells - cytology

Mice

ADAM Proteins - genetics

src-Family Kinases - genetics

Fetal Blood

Receptor, Fibroblast Growth Factor, Type 2 - genetics

Cell Movement

Keratinocytes - physiology

Mitogen-Activated Protein Kinase 1 - metabolism

Details

Title: Subtitle: Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17
Creators: Thorsten Maretzky - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery at Weill Medical College, Cornell University, New York, New York 10021, USA
Astrid Evers
Wenhui Zhou
Steven L Swendeman
Pui-Mun Wong
Shahin Rafii
Karina Reiss
Carl P Blobel
Resource Type: Journal article
Publication Details: Nature communications, Vol.2(1), pp.229-229
DOI: 10.1038/ncomms1232
PMID: 21407195
PMCID: PMC3074487
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: R01 EY015719 / NEI NIH HHS C06 RR012538 / NCRR NIH HHS GM64750 / NIGMS NIH HHS R01 GM064750-09 / NIGMS NIH HHS R01 GM064750 / NIGMS NIH HHS C06-RR12538-01 / NCRR NIH HHS EY015719 / NEI NIH HHS
Language: English
Date published: 2011
Academic Unit: Internal Medicine
Record Identifier: 9984094575702771

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