The role of the fibronectin IGD motif in stimulating fibroblast migration.
The motogenic activity of migration-stimulating factor, a truncated isoform of fibronectin (FN), has been attributed to the IGD motifs present in its FN type 1 modules. The structure-function relationship of various recombinant IGD-containing FN fragments is now investigated. Their structure is assessed by solution state NMR and their motogenic ability tested on fibroblasts. Even conservative mutations in the IGD motif are inactive or have severely reduced potency, while the structure remains essentially the same. A fragment with two IGD motifs is 100 times more active than a fragment with one and up to 10(6) times more than synthetic tetrapeptides. The wide range of potency in different contexts is discussed in terms of cryptic FN sites and cooperativity. These results give new insight into the stimulation of fibroblast migration by IGD motifs in FN.
Millard
Christopher J
CJ
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
Ellis
Ian R
IR
Pickford
Andrew R
AR
Schor
Ana M
AM
Schor
Seth L
SL
Campbell
Iain D
ID
D020816:Amino Acid Motifs; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D005347:Fibroblasts; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D020033:Protein Isoforms; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D005353:Fibronectins; D020033:Protein Isoforms; D011994:Recombinant Proteins