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 a synthetic 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 intracellular point 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.
Borich
S M
SM
School of Biological Sciences, University of Auckland, New Zealand.
Englebretsen
D
D
Harding
D R
DR
Scott
G K
GK
D000595:Amino Acid Sequence; D001839:Bombesin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts; D006801:Humans; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000187:drug effects / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D018179:Receptors, Thrombin / Q000378:metabolism*; D015290:Second Messenger Systems; D013917:Thrombin / Q000494:pharmacology
D009842:Oligopeptides; D011480:Protease Inhibitors; D018179:Receptors, Thrombin; D004815:Epidermal Growth Factor; D010450:Endopeptidases; D013917:Thrombin; D001839:Bombesin