Multi-factorial modulation of IGD motogenic potential in MSF (migration stimulating factor).
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.
Ellis
Ian R
IR
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
Jones
Sarah J
SJ
Staunton
David
D
Vakonakis
Ioannis
I
Norman
David G
DG
Potts
Jennifer R
JR
Milner
Caroline M
CM
Meenan
Nicola A G
NA
Raibaud
Sophie
S
Ohea
Go
G
Schor
Ana M
AM
Schor
Seth L
SL
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
D016207:Cytokines; C067625:FN1 protein, human; D005353:Fibronectins; D020409:Molecular Motor Proteins; D010446:Peptide Fragments