title: Multi-factorial modulation of IGD motogenic potential in MSF (migration stimulating factor).
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.
authors.affiliation: Unit of Cell and Molecular Biology, The Dental School, College of Medicine, Dentistry and Nursing, University of Dundee, Park Place, DD1 4 HR, UK. irellis@dundee.ac.uk
authors.forename: Ian R
authors.initials: IR
authors.lastname: Ellis
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Jones
authors.forename: David
authors.initials: D
authors.lastname: Staunton
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vakonakis
authors.forename: David G
authors.initials: DG
authors.lastname: Norman
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Potts
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Milner
authors.forename: Nicola A G
authors.initials: NA
authors.lastname: Meenan
authors.forename: Sophie
authors.initials: S
authors.lastname: Raibaud
authors.forename: Go
authors.initials: G
authors.lastname: Ohea
authors.forename: Ana M
authors.initials: AM
authors.lastname: Schor
authors.forename: Seth L
authors.initials: SL
authors.lastname: Schor
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008297:Male; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D016207:Cytokines; C067625:FN1 protein, human; D005353:Fibronectins; D020409:Molecular Motor Proteins; D010446:Peptide Fragments