Interactions with CS/DS divert Fgf2 signalling towards migration Free

Fibroblast growth factor 2 (Fgf2) activates multiple signalling pathways, and can have important roles in proliferation, migration, differentiation and cell repair. The biological activity of Fgf2 depends on glycosaminoglycans, such as chondroitin and dermatan sulfates (CS/DS), as co-receptors. Uronyl 2-O-sulfotransferase (Ust) catalyses the addition of sulfate groups at C2 of L-iduronic acid and D-glucuronic acid of CS/DS and, in this study (p.460), Daniela Gabriele Seidler and colleagues investigate the role of Ust-mediated sulfation in Fgf2-induced cell migration. The authors show that overexpressing Ust in CHO-K1 cells increases CS/DS 2-O sulfation, whereas Ust knockdown abolishes the sulfation. Increased CS/DS sulfation altered Fgf2 binding and increased phosphorylation of ERK1/2; these changes then led to enhanced cell migration and paxillin activation. Conversely, Ust knockdown and inhibition of sulfation or Fgf receptor resulted in the loss of migration, as did the lack of the proteoglycan syndecan 1. These findings demonstrate a new role for cell-surface CS/DS in Fgf2-induced cell migration.