THROMBIN RECEPTOR AND ENDOGENOUS GROWTH-RELATED PROTEOLYSIS IN HUMAN FIBROBLASTS

We have previously shown that thrombin reverses the growth inhibition caused in human fibroblasts when a cell-surface proteinase is inhibited. A similar result was obtained with asynthetic thrombin receptor agonist peptide, which mimics the conformational change resulting from receptor cleavage by thrombin. Consideration of the effects of the growth-related proteinase on intracellular second messengers indicates that cleavage of the thrombin receptor by this endogenous proteinase is not a significant event for normal fibroblast growth in culture. Inhibition of the growth-related proteinase also fails to block the mitogenic action of bombesin. In conjunction with earlier results, this suggests that the intracellularpoint of action of GRP inhibition may be at, or closely connected with, the receptor-linked tyrosine kinases, and evidence for inhibition of protein phosphorylation following from GRP inhibition is presented. © 1994 Academic Press. All rights reserved.