title: A dimeric form of lipocortin-1 in human placenta.
abstract: We have characterized a 68 kDa lipocortin from human placenta that was identified as a covalently linked homodimer of lipocortin-1 by peptide mapping and sequence analysis. The site of cross-linking was localized within the 3 kDa N-terminal tail region, an exposed domain that contains the phosphorylation sites for protein tyrosine kinase and protein kinase C and is sensitive to proteolysis. Sequence analysis of the corresponding peptide revealed that glutamine-18 was modified, suggesting that the cross-link may be generated by a transglutaminase. By incubating lipocortin-1 with placental membranes and with labelled glycine ethyl ester we observed a Ca2+-dependent labelling of lipocortin-1 within the tail region, supporting this notion. Like lipocortin-1, the dimer inhibits phospholipase Ad2 activity, is a substrate for the epidermal-growth-factor (EGF) receptor/kinase, and display Ca2+-dependent binding to phosphatidylserine-containing vesicles. In preparations from human placenta the dimer is particularly abundant, accounting for approx. 20% of the lipocortin-1.
authors.affiliation: Biogen Inc., Cambridge, MA 02142.
authors.forename: R B
authors.initials: RB
authors.lastname: Pepinsky
authors.forename: L K
authors.initials: LK
authors.lastname: Sinclair
authors.forename: E P
authors.initials: EP
authors.lastname: Chow
authors.forename: B
authors.initials: B
authors.lastname: O'Brine-Greco
mesh_terms: D000595:Amino Acid Sequence; D017302:Annexins; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D003488:Cyanogen Bromide; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011108:Polymers; D011247:Pregnancy; D011487:Protein Conformation
chemical_list: D017302:Annexins; D002135:Calcium-Binding Proteins; D003432:Cross-Linking Reagents; D006023:Glycoproteins; D011108:Polymers; D003488:Cyanogen Bromide