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Integrin αvβ3 binding to α5-laminins facilitates FGF-2 and VEGF induced proliferation of human ECV304 cells
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology.
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URN: urn:nbn:se:uu:diva-89675OAI: oai:DiVA.org:uu-89675DiVA: diva2:161350
Available from: 2002-03-11 Created: 2002-03-11 Last updated: 2010-01-13Bibliographically approved
In thesis
1. The Laminins and their Receptors
Open this publication in new window or tab >>The Laminins and their Receptors
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Basement membranes are thin extracellular sheets that surround muscle, fat and peripheral nerve cells and underlay epithelial and endothelial cells. Laminins are one of the main protein families of these matrices. Integrins and dystroglycan are receptors for laminins, connecting cells to basement membranes. Each laminin consists of three different chains, (α, β, γ). Laminin-1 (α1β1γ1) was the first laminin to be found and is the most frequently studied. Despite this, it was unclear where its α1 chain was expressed. A restricted distribution of the α1 chain in the adult epithelial basement membranes was demonstrated in the present study. In contrast, dystroglycan was found to have a much broader distribution. Dystroglycan is an important receptor for α2-laminins in muscle, but binds also α1-laminins. The more ubiquitous α5-laminins were also shown to bind dystroglycan, but with distinctly lower affinity than α1- and α2- laminins.

The biological roles of different laminin isoforms have been investigated. Differences were found in the capacity of various tested laminins to promote epithelial cell adhesion. The α5-laminins were potent adhesive substrates, a property shown to be dependent on α3 and α6 integrins. Each receptor alone could promote efficient epithelial cell adhesion to α5-laminins. Yet, only α6 integrin and in particular the α6A cytoplasmic splice variant could be linked to laminin-mediated activation of a mitogen-activated protein kinase (MAP kinase) pathway. Attachment to either α1- or α5-laminins activated extracellular-signal regulated kinase (ERK) in cells expressing the integrin α6A variant, but not in cells expressing α6B. A new role for dystroglycan as a suppressor of this activation was demonstrated. Dystroglycan antibodies, or recombinant fragments with high affinity for dystroglycan, decreased ERK activation induced by integrin α6 antibodies. Integrin αvβ3 was identified as a novel co-receptor for α5-laminin trimers. Cell attachment to α5-laminins was found to facilitate growth factor induced cell proliferation. This proliferation could be blocked by antibodies against integrin αvβ3 or by an inhibitor of the MEK/ERK pathway. Therefore, integrin αvβ3 binding to α5-laminins could be of biological significance.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 67 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 688
Cell and molecular biology, Basement membrane, laminin, integrin, dystroglycan, epithelial cells, signal transduction, Cell- och molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Cellbiology
urn:nbn:se:uu:diva-1771 (URN)91-554-5239-6 (ISBN)
Public defence
2002-03-16, B22 (BMC), Uppsala, 10:00
Available from: 2002-03-11 Created: 2002-03-11Bibliographically approved

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