title: Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene.
abstract: Polycystin-1 (PC1), the PKD1 gene product, plays a critical role in renal tubule diameter control and disruption of its function causes cyst formation in human autosomal dominant polycystic kidney disease. Recent evidence shows that PC1 undergoes cleavage at the juxtamembrane G protein-coupled receptor proteolytic site (GPS), a process likely to be essential for its biological activity. Here we further characterized the proteolytic cleavage of PC1 at the GPS domain. We determined the actual cleavage site to be between leucine and threonine of the tripeptide HLT(3049) of human PC1. Cleavage occurs in the early intracellular secretory pathway and requires initial N-glycan attachment but not its subsequent trimming. We provide evidence that the cleavage occurs via a cis-autoproteolytic mechanism involving an ester intermediate as shown for Ntn hydrolases and EMR2.
authors.affiliation: Division of Nephrology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Wei
authors.forename: Karl
authors.initials: K
authors.lastname: Hackmann
authors.forename: Hangxue
authors.initials: H
authors.lastname: Xu
authors.forename: Gregory
authors.initials: G
authors.lastname: Germino
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D017931:DNA Primers; D004285:Dogs; D006031:Glycosylation; D006801:Humans; D007668:Kidney; D007684:Kidney Tubules / Q000473:pathology; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000473:pathology; D018035:Receptors, Odorant / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D018035:Receptors, Odorant; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050396:TRPP Cation Channels; C077170:G-protein coupled receptor OR3