The role of syndecan cytoplasmic domain in basic fibroblast growth factor-dependent signal transduction.
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.
Volk
R
R
Angiogenesis Research Center, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Schwartz
J J
JJ
Li
J
J
Rosenberg
R D
RD
Simons
M
M
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
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