Processing of the major pancreatic zymogen granule membrane protein, GP2.
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.
Fritz
Benjamin A
BA
The Department of Medicine and Digestive Disease Center, Stanford University, Stanford, California 94305-5187, USA.
Poppel
Clinton S
CS
Fei
Matthew W
MW
Lowe
Anson W
AW
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
C489339:GP2 protein, human; D058851:GPI-Linked Proteins; C066161:Gp2 protein, rat; D008562:Membrane Glycoproteins