The role of syndecan cytoplasmic domain in basic fibroblast growth factor-dependent signal transduction

To determine the role played by syndecan-4 cytoplasmic mic domain in the me diation of basic fibroblast growth factor (bFGF) signaling, immortalized hu man cells (ECV) were used to generate cell lines expressing constructs enco ding full-length sequences for syndecan-4 (S4), syndecan-1 (S1), glypican-1 (G1), or chimeric proteins consisting of the ectoplasmic domain of glypica n-1 linked to the transmembrane/cytoplasmic domain of syndecan-4 (G1-S4c) a nd the ectoplasmic domain of syndecan-4 linked to the glypican-1 glycosylph osphatidylinositol (GPI) anchor sequence (S4-GPI). Vector-transduced cells (VC) were used as controls. Expression of all these proteoglycans (except f or the vector control) significantly increased cell-associated heparan sulf ate mass and the number of low affinity bFGF-binding sites. However, in low serum medium, the addition of bFGF stimulated growth and migration of cell s expressing S4 and G1-S4c constructs but not G1, S1, S4-GPI, or VC cells. Similar results were obtained using Matrigel growth assays. Mutations of he paran sulfate attachment sites on S4 construct abolished syndecan-4-depende nt augmentation of bFGF responses. We conclude that cytoplasmic tail of syn decan-4 plays an important role in bFGF-mediated signal transduction.