title: Characterization of meFucoidan as a selective inhibitor for secretory phospholipase A2-IIA and the phosphorylation of meFucoidan-binding proteins by A-kinase in vitro.
abstract: The direct interaction of Mekabu fucoidan (meFucoidan) with four functional basic proteins (sPLA2-IIA, bFGF, histone H2B and HBV core protein) and three synthetic FGF-BP peptides (sp5, GE13 and RS6) was characterized in vitro. It was found that (i) meFucoidan inhibited dose-dependently the activity of sPLA2-IIA, but not pPLA2, through its direct binding to the enzyme; (ii) sPLA2-IIA activity was sensitive to meFucoidan rather than heparin, but significantly stimulated by sulfatide; (iii) the A-kinase-mediated phosphorylation of these basic proteins, except sPLA2-IIA, and synthetic peptides, containing potent phosphorylation sites for A-kinase, was inhibited dose-dependently by meFucoidan; and (iv) two consensus meFucoidan-binding motifs (B-B-B-B-X and B-X-B-B-X; B, basic amino acid) in these basic proteins and synthetic peptides could be overlapping to the potent phosphorylation site (B-B-X-S/T) for the kinase in vitro. These results presented here suggest that meFucoidan functions as a selective inhibitor for sPLA2-IIA and the A-kinase-mediated phosphorylation of cellular meFucoidan-binding functional basic proteins in vitro.
authors: Laboratory of Pathology, Graduate School of Medical Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. maruyama@ahs.kitasato-u.ac.jp
authors: Hiroko
authors: H
authors: Maruyama
authors: Kanzo
authors: K
authors: Suzuki
authors: Sayaka
authors: S
authors: Miyai
authors: Kenzo
authors: K
authors: Ohtsuki
mesh_terms: D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D010766:Phosphorylation; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D044648:Undaria / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D064801:Phospholipase A2 Inhibitors; D011134:Polysaccharides; D011994:Recombinant Proteins; D013433:Sulfoglycosphingolipids; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D017868:Cyclic AMP-Dependent Protein Kinases; D054501:Group II Phospholipases A2; D054467:Phospholipases A2