title: Processing of the major pancreatic zymogen granule membrane protein, GP2.
abstract: BACKGROUND
  The pancreatic exocrine secretory granule, the zymogen granule, releases digestive enzymes into the intestine. GP2 is the most abundant zymogen granule membrane protein. Coincident with exocrine secretion, GP2 is released from the membrane and secreted into the pancreatic duct.
  
  
  OBJECTIVE
  To characterize changes in the structure of GP2 as it progresses through the secretory pathway.
  
  
  METHODS
  Polarized MDCK cells that express the rat GP2 gene were used to examine the sequential processing of the polypeptide backbone.
  
  
  RESULTS
  Within the cell, GP2 is initially proteolytically processed from a 55- to a 53-kd form at or before the trans-Golgi network. The protein is then processed to a 51-kd form, which is found on the apical plasma membrane and in secretions. Similar processing was also observed in primary rat pancreatic cultures and in MDCK cells that express human GP2. The amino-terminal sequence of human GP2 derived from pancreatic secretions was determined for two human patients and began at Gly39, revealing a potential processing site.
  
  
  CONCLUSIONS
  In contrast to other digestive enzymes secreted by the pancreas that are activated by proteolysis in the intestine, GP2 undergoes sequential intracellular cleavage. Alterations in GP2 structure by proteolysis may regulate GP2 function at specific sites within the pancreatic cell.
authors.affiliation: The Department of Medicine and Digestive Disease Center, Stanford University, Stanford, California 94305-5187, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Fritz
authors.forename: Clinton S
authors.initials: CS
authors.lastname: Poppel
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Fei
authors.forename: Anson W
authors.initials: AW
authors.lastname: Lowe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D013696:Temperature
chemical_list: C489339:GP2 protein, human; D058851:GPI-Linked Proteins; C066161:Gp2 protein, rat; D008562:Membrane Glycoproteins