title: The role of syndecan cytoplasmic domain in basic fibroblast growth factor-dependent signal transduction.
abstract: To determine the role played by syndecan-4 cytoplasmic domain in the mediation of basic fibroblast growth factor (bFGF) signaling, immortalized human cells (ECV) were used to generate cell lines expressing constructs encoding full-length sequences for syndecan-4 (S4), syndecan-1 (S1), glypican-1 (G1), or chimeric proteins consisting of the ectoplasmic domain of glypican-1 linked to the transmembrane/cytoplasmic domain of syndecan-4 (G1-S4c) and the ectoplasmic domain of syndecan-4 linked to the glypican-1 glycosylphosphatidylinositol (GPI) anchor sequence (S4-GPI). Vector-transduced cells (VC) were used as controls. Expression of all these proteoglycans (except for the vector control) significantly increased cell-associated heparan sulfate mass and the number of low affinity bFGF-binding sites. However, in low serum medium, the addition of bFGF stimulated growth and migration of cells 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 heparan sulfate attachment sites on S4 construct abolished syndecan-4-dependent augmentation of bFGF responses. We conclude that cytoplasmic tail of syndecan-4 plays an important role in bFGF-mediated signal transduction.
authors.affiliation: Angiogenesis Research Center, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: R
authors.initials: R
authors.lastname: Volk
authors.forename: J J
authors.initials: JJ
authors.lastname: Schwartz
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: R D
authors.initials: RD
authors.lastname: Rosenberg
authors.forename: M
authors.initials: M
authors.lastname: Simons
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003593:Cytoplasm; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D011509:Proteoglycans / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D053671:Syndecan-4
chemical_list: D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011493:Protein Kinase C; D011509:Proteoglycans; D053671:Syndecan-4; C508304:SDC4 protein, human