title: Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol proteinase and a lysosomal aspartyl proteinase.
abstract: BHK cells expressing human lysosomal acid phosphatase (LAP) transport LAP to lysosomes as an integral membrane protein. In lysosomes LAP is released from the membrane by proteolytic processing, which involves at least two cleavages at the C terminus of LAP. The first cleavage is catalysed by a thiol proteinase at the outside of the lysosomal membrane and removes the bulk of the cytoplasmic tail of LAP. The second cleavage is catalysed by an aspartyl proteinase inside the lysosomes and releases the luminal part of LAP from the membrane-spanning domain. The first cleavage at the cytoplasmic side of the lysosomal membrane depends on acidification of lysosomes and the second cleavage inside the lysosomes depends on prior processing of the cytoplasmic tail. These results suggest that the cytoplasmic tail controls the conformation of the luminal portion of LAP and vice versa.
authors.affiliation: University of Göttingen, Biochemie II, FRG.
authors.forename: S
authors.initials: S
authors.lastname: Gottschalk
authors.forename: A
authors.initials: A
authors.lastname: Waheed
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: P
authors.initials: P
authors.lastname: Laidler
authors.forename: K
authors.initials: K
authors.lastname: von Figura
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism*; D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases; D002460:Cell Line; D002498:Centrifugation; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000201:enzymology*; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D008565:Membrane Proteins; D011498:Protein Precursors; D000135:Acid Phosphatase; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D016282:Aspartic Acid Endopeptidases