GTP gamma S-induced pepsinogen secretion from gastric chief cells does not require carboxyl methylation or translocation of low molecular weight (LMW) GTP-binding proteins.

We identified at least four LMW GTP-binding proteins in membrane and cytosolic fractions from dispersed gastric chief cells. Extraction of membrane-bound GTP-binding proteins with various agents revealed that these proteins are intimately associated with chief cell membranes. Upon extraction with Triton X-114, the majority of GTP-binding proteins partitioned into the detergent phase, indicative of their hydrophobic nature. Although carboxyl methylation of LMW GTP-binding proteins has been shown to regulate their localization and function, inhibitors of carboxyl methylation had no effect on GTP gamma S-induced pepsinogen secretion. Moreover, pre-permeabilization of chief cells for up to 20 min did not alter GTP gamma S-induced secretion, suggesting that the guanine nucleotide analogue interacts with membrane-bound GTP-binding proteins to elicit a secretory response.