title: The efficiency of the uncleaved secretion signal in the plasminogen activator inhibitor type 2 protein can be enhanced by point mutations that increase its hydrophobicity.
abstract: Plasminogen-activator inhibitor type 2 (PAI-2) is a specific inhibitor of plasminogen activators that belongs to the serine protease inhibitor superfamily (SERPINS). PAI-2 exists in two molecular forms: an intracellular, non-glycosylated form and a secreted, glycosylated form. Like ovalbumin, PAI-2 contains an uncleaved internal secretion signal. By deletion analysis, we have mapped the secretion signal to two mildly hydrophobic regions near the NH2 terminus. We also show that both of these regions become more efficient translocation signals when their hydrophobicities are increased. The PAI-2 secretion signal provides a unique example of a signal that, by virtue of its poor efficiency, allows the synthesis of both an extracellular and an intracellular form of the protein.
authors.affiliation: Department of Molecular Biology, Karolinska Institute, Huddinge, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: von Heijne
authors.forename: P
authors.initials: P
authors.lastname: Liljeström
authors.forename: P
authors.initials: P
authors.lastname: Mikus
authors.forename: H
authors.initials: H
authors.lastname: Andersson
authors.forename: T
authors.initials: T
authors.lastname: Ny
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D008969:Molecular Sequence Data; D009154:Mutation; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015843:Serpins / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D015849:Plasminogen Inactivators; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D015843:Serpins; D012313:RNA; D004247:DNA