Not All Perlecans Are Created Equal INTERACTIONS WITH FIBROBLAST GROWTH FACTOR (FGF) 2 AND FGF RECEPTORS

摘要: Human basement membrane heparan sulfate proteoglycan (HSPG) perlecan binds and activates fibroblast growth factor (FGF)-2 through its (HS) chains. Here we show that perlecans immunopurified from three cellular sources possess different HS structures subsequently FGF-2 binding activating capabilities. Perlecan isolated human umbilical arterial endothelial cells (HUAEC) a continuous cell line (C11 STH) bound similar amounts of either alone or complexed with FGFRα1-IIIc FGFR3α-IIIc. Both stimulated the BaF3 lines expressing FGFR1b/c; however, only HUAEC those FGFR3c, suggesting source confers FGF FGFR specificity. Despite these differences in activation, level 2-O-and 6-O-sulfation was for both perlecans. Interestingly, colon carcinoma capable incapable any unless removed protein core. The chains also exhibited greater bioactivity after digestion heparinase III. Collectively, data clearly demonstrate decorating single PG is dependent on subtle changes structure including secondary interactions have profound effect biological activity.