Regulation of syndecan-4 phosphorylation in vivo.
Recent studies suggest that some of the heparan sulfate-carrying proteoglycans may directly participate in signaling via their cytoplasmic tail. The present investigation addresses the potential involvement of syndecan-4, a widely expressed transmembrane proteoglycan, in this process. We found that the cytoplasmic tail of syndecan-4 is phosphorylated on a single serine residue (Ser183) in growth-arrested NIH 3T3 fibroblasts, with a stoichiometry of 0.3 mol Pi/mol syndecan-4. Treatment of the cells with a protein kinase C (PKC)-activating phorbol ester lead to a 2.5-fold increase in Ser183 phosphorylation. This increase was inhibited by a generic PKC inhibitor but not by an inhibitor specific to the calcium-dependent conventional PKCs, suggesting that the cytoplasmic tail of syndecan-4 is phosphorylated by a calcium-independent novel PKC isozyme. Application of 10-30 ng/ml basic fibroblast growth factor (bFGF) produced a 2-3-fold reduction in the phosphorylation of syndecan-4. Because treatment with the phosphatase inhibitor calyculin prevented the bFGF-induced decrease in syndecan-4 phosphorylation, the effect of bFGF appears to be mediated by a protein serine/threonine phosphatase type 1 or 2A. We conclude that the cytoplasmic tail of syndecan-4 is subject to in vivo phosphorylation on Ser183, which is regulated by the activities of a novel PKC isozyme and a bFGF-dependent serine/threonine phosphatase.
Horowitz
A
A
Angiogenesis Research Center, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Simons
M
M
D016475:3T3 Cells; D000470:Alkaloids; D000595:Amino Acid Sequence; D000818:Animals; D053119:Benzophenanthridines; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010617:Phenanthridines / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D053671:Syndecan-4
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D010617:Phenanthridines; D011509:Proteoglycans; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; C016299:chelerythrine; D011493:Protein Kinase C