title: Vg1 has specific processing requirements that restrict its action to body axis patterning centers.
abstract: Unlike most transforming growth factor-beta (TGF-beta) superfamily members, Vg1 has been shown not to produce gross phenotypic alterations in Xenopus embryos when overexpressed by mRNA injection. Experiments with artificial chimeric constructs and a recently identified second allele of Vg1 suggest that this may be due to unusually stringent requirements for proteolytic processing. We provide biological and biochemical evidence that cleavage by two distinct proteolytic enzymes is required for effective activation of Vg1. We demonstrate a tightly restricted overlap in expression patterns of Vg1 with the proteases required to release the mature peptide. The data presented may account for the long-standing observation that the vast majority of Vg1 protein, in vivo, is present in its unprocessed form. Taken together, these observations provide a plausible mechanism for local action of Vg1 consistent with requirements imposed by current models of pattern formation in the developing body axis.
authors: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA. john.thomas@fda.hhs.gov
authors: John Terrig
authors: JT
authors: Thomas
authors: Malcolm
authors: M
authors: Moos
mesh_terms: D000483:Alleles; D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006868:Hydrolysis; D045702:Proprotein Convertase 5 / Q000502:physiology; D012333:RNA, Messenger; D012697:Serine Endopeptidases / Q000502:physiology; D013379:Substrate Specificity; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014981:Xenopus / Q000196:embryology* / Q000378:metabolism; D029867:Xenopus Proteins / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; C513103:GDF1 protein, Xenopus; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C513085:PCSK6 protein, Xenopus; D045702:Proprotein Convertase 5; D012697:Serine Endopeptidases