Journal article
Opposing Roles of Integrin α6Aβ1 and Dystroglycan in Laminin-mediated Extracellular Signal-regulated Kinase Activation
Molecular biology of the cell, Vol.14(5), pp.2088-2103
05/2003
DOI: 10.1091/mbc.e03-01-0852
PMCID: PMC165099
PMID: 12802077
Abstract
Laminin–integrin interactions can in some settings activate the extracellular signal-regulated kinases (ERKs) but the control mechanisms are poorly understood. Herein, we studied ERK activation in response to two laminins isoforms (-1 and -10/11) in two epithelial cell lines. Both cell lines expressed β1-containing integrins and dystroglycan but lacked integrin α6β4. Antibody perturbation assays showed that both cell lines bound to laminin-10/11 via the α3β1and α6β1 integrins. Although laminin-10/11 was a stronger adhesion complex than laminin-1 for both cell lines, both laminins activated ERK in only one of the two cell lines. The ERK activation was mediated by integrin α6β1 and not by α3β1 or dystroglycan. Instead, we found that dystroglycan-binding domains of both laminin-1 and -10/11 suppressed integrin α6β1-mediated ERK activation. Moreover, the responding cell line expressed the two integrin α6 splice variants, α6A and α6B, whereas the nonresponding cell line expressed only α6B. Furthermore, ERK activation was seen in cells transfected with the integrin α6A subunit, but not in α6B-transfected cells. We conclude that laminin-1 and -10/11 share the ability to induce ERK activation, that this is regulated by integrin α6Aβ1, and suggest a novel role for dystroglycan-binding laminin domains as suppressors of this activation.
Details
- Title: Subtitle
- Opposing Roles of Integrin α6Aβ1 and Dystroglycan in Laminin-mediated Extracellular Signal-regulated Kinase Activation
- Creators
- Maria Ferletta - Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, Sweden, Department of Cell and Molecular Biology, Uppsala University, SE-75123 Uppsala, SwedenYamato Kikkawa - Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, Sweden, Department of Cell and Molecular Biology, Uppsala University, SE-75123 Uppsala, SwedenHao Yu - Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, SwedenJan F Talts - Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, SwedenMadeleine Durbeej - Department of Physiology, Biophysics, and Neurology, Howard Hughes Medical Institute, University of Iowa, Iowa City, IowaArnoud Sonnenberg - The Netherlands Cancer Institute, Amsterdam, The NetherlandsRupert Timpl - Max-Planck-Institute for Biochemistry, Martinsried, GermanyKevin P Campbell - Department of Physiology, Biophysics, and Neurology, Howard Hughes Medical Institute, University of Iowa, Iowa City, IowaPeter Ekblom - Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, Sweden, Department of Cell and Molecular Biology, Uppsala University, SE-75123 Uppsala, SwedenElke Genersch - Department of Cell and Molecular Biology, Lund University, SE-22184 Lund, Sweden, Department of Cell and Molecular Biology, Uppsala University, SE-75123 Uppsala, Sweden
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.14(5), pp.2088-2103
- DOI
- 10.1091/mbc.e03-01-0852
- PMID
- 12802077
- PMCID
- PMC165099
- NLM abbreviation
- Mol Biol Cell
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Publisher
- American Society for Cell Biology
- Language
- English
- Date published
- 05/2003
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020868902771
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