CHANGES IN LEVELS OF PANCREATIC ENDOPLASMIC-RETICULUM PROTEINS THAT FUNCTION IN TRANSLOCATION AND MATURATION OF SECRETORY PROTEINS IN RESPONSE TO CHOLECYSTOKININ

Two pathways operate to target newly-synthesised proteins to the endop lasmic reticulum. In one, the signal recognition particle attaches to the signal sequences of nascent chains on ribosomes and slows or stops translation until contact is made with the docking protein at the mem brane. The second operates via molecular chaperons. The pathways conve rge at the level of a 43 kDa signal binding protein integrated into th e membrane, where translocation through a proteinaceous pore is initia ted. In the lumen, proteins fold and disulphide formation is catalysed by the enzyme protein disulphide isomerase. The heavy chain binding p rotein may attach to unassembled or unfolded proteins and prevent thei r exit from the ER to the Golgi. Cholecystokinin (CCK) treatment incre ases the biosynthesis and secretion of pancreatic proteins, increases the levels of PDI and the 43 kDa binding protein, and reduces levels o f BiP. These proteins may be possible targets for genetic manipulation to improve processing of heterologous proteins from cultured mammalia n cells.