title: Multiple forms of basic fibroblast growth factor: amino-terminal cleavages by tumor cell- and brain cell-derived acid proteinases.
abstract: Basic fibroblast growth factor (FGF) was purified by heparin-Sepharose chromatography from two sources, brain and hepatoma cells. Brain cell-derived basic FGF (brFGF) and hepatoma cell-derived basic FGF (heFGF) were found to exist in multiple forms whose molecular weights depended on whether they were extracted from their respective tissue or cells at neutral or acid pH. When extracted at pH 7.0 brFGF and heFGF comigrated on NaDodSO4/PAGE with a Mr of approximately 18,400. When extracted at pHs 3.5-4.5, acid proteinases cleaved brFGF and heFGF to lower molecular weight forms but to different extents. brFGF was cleaved to a Mr 18,000 form at acid pH by a brain-derived acid proteinase that could be inhibited by pepstatin. heFGF was cleaved mostly to a Mr 16,500 form at acid pH by a hepatoma cell-derived acid proteinase that was inhibited by leupeptin. Electrophoretic transfer blot analysis using site-specific anti-FGF antibodies suggested that the cleavages occurred at the amino-terminal ends of brFGF and heFGF. Cleavage to lower molecular weight forms of brFGF and heFGF did not affect growth factor activity or chromatographic behavior on heparin-Sepharose columns.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001921:Brain / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D010450:Endopeptidases / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000502:physiology
chemical_list: D007976:Leupeptins; D011480:Protease Inhibitors; D005346:Fibroblast Growth Factors; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C032854:leupeptin