Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor) |
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Authors: | Ian R Ellis Sarah J Jones Ioannis Vakonakis David G Norman Caroline M Milner Sophie Raibaud Ana M Schor |
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Institution: | a Unit of Cell and Molecular Biology, The Dental School, College of Medicine, Dentistry and Nursing, University of Dundee, Park Place, DD1 4 HR, UK b Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK c Paul Scherrer Institut, 5232 Villigen PSI, Switzerland d The CRUK Nucleic Acid Structure Research Group, The College of Life Sciences, MSI/WTB Complex, University of Dundee, Dow St. Dundee, DD1 5EH, UK e Department of Biology, University of York, York YO10 5YW, UK f Department of Chemistry, University of York, York YO10 5DD, UK g Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK |
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Abstract: | Migration Stimulating Factor (MSF) is a genetically truncated isoform of fibronectin (Fn). MSF is a potent stimulator of fibroblast migration, whereas full length Fn is devoid of motogenic activity. MSF and Fn contain four IGD motifs, located in the 3rd, 5th, 7th and 9th type I modules; these modules are referred to as 3FnI, 5FnI, 7FnI and 9FnI, respectively. We have previously reported that mutation of IGD motifs in modules 7FnI and 9FnI of MSF is sufficient to completely abolish the motogenic response of target adult skin fibroblasts. We now report that the IGD sequences in 3FnI and 5FnI are also capable of exhibiting motogenic activity when present within fragments of MSF. When present within 1-5FnI, these sequences require the presence of serum or vitronectin for their motogenic activity to be manifest, whereas the IGD sequences in 7FnI and 9FnI are bioactive in the absence of serum factors. All MSF and IGD-containing peptides stimulated the phosphorylation of the integrin binding protein focal adhesion kinase (FAK) but did not necessarily affect migration. These results suggest that steric hindrance determines the motogenic activity of MSF and Fn, and that both molecules contain cryptic bioactive fragments. |
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Keywords: | Cell motility Fibronectin Fibroblasts |
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