title: A Serpin family gene, protease nexin-1 has an activity distinct from protease inhibition in early Xenopus embryos.
abstract: Protease nexin-1 (PN-1)/glia-derived nexin (GDN) is a member of the Serpin (serine proteinase inhibitor) family, and can inhibit thrombin, plasmin, and plasminogen activators. PN-1 has been shown to be a neuroprotective factor in a number of assay systems, and this activity has been assumed to be a function of its protease inhibitory function. Here, we report cloning and characterization of a Xenopus orthologue of PN-1 (xPN-1). xPN-1 was isolated in a functional screen of an egg cDNA library for factors that modify early axial patterning. xPN-1 is expressed maternally through late tadpole stages, and is expressed preferentially in the notochord, the pharyngeal endoderm, the otic vesicle, and the ventral region of the brain in tailbud embryos. Over-expression of xPN-1 causes defective gastrulation, inhibits convergent extension movements in activin induced animal caps, and inhibits expression of a distinct subset of activin induced mesendodermal markers. Interestingly, expression of point or deletion mutation of the Reactive Center Loop of xPN1,which is essential for the protease inhibitory activity of all serpins, had effects on Xenopus development indistinguishable from those of wild type xPN-1. These observations suggest the possibility that xPN-1 has a novel activity in addition to its established function as an inhibitor of serine proteases.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston MA 02115, USA.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Onuma
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Malcolm
authors.initials: M
authors.lastname: Whitman
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D019521:Body Patterning; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D015843:Serpins