Multi-factorial modulation of IGD motogenic potential in MSF (Migration Stimulating Factor)

Ian R. Ellis (Lead / Corresponding author), Sarah J. Jones, David Staunton, Ioannis Vakonakis, David G. Norman, Jennifer R. Potts, Caroline M. Milner, Nicola A. G. Meenan, Sophie Raibaud, Go Ohea, Ana M. Schor, Seth L. Schor

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    9 Citations (Scopus)

    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 (3)FnI, (5)FnI, (7)FnI and (9)FnI, respectively. We have previously reported that mutation of IGD motifs in modules (7)FnI and (9)FnI of MSF is sufficient to completely abolish the motogenic response of target adult skin fibroblasts. We now report that the IGD sequences in (3)FnI and (5)FnI are also capable of exhibiting motogenic activity when present within fragments of MSF. When present within (1-5)FnI, these sequences require the presence of serum or vitronectin for their motogenic activity to be manifest, whereas the IGD sequences in (7)FnI and (9)FnI 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. (C) 2010 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)2465-2476
    Number of pages12
    JournalExperimental Cell Research
    Volume316
    Issue number15
    DOIs
    Publication statusPublished - 10 Sep 2010

    Keywords

    • Cell motility
    • Fibronectin
    • Fibroblasts
    • STAPHYLOCOCCUS-AUREUS FNBPA
    • GELATIN-BINDING DOMAIN
    • TANDEM BETA-ZIPPER
    • HUMAN FIBRONECTIN
    • FIBROBLAST MIGRATION
    • CRYSTAL-STRUCTURES
    • CELL MOTILITY
    • MATRIX
    • ADHESION
    • RECEPTOR

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