Thrombin receptor agonist peptide induction of mitogenesis in CCL39 cells.
The role of the thrombin receptor tethered ligand hypothesis in mediating the mitogenic responses of cells to thrombin was explored. We have found that small (5-14 amino acid) peptides corresponding to the proposed amino terminus of thrombin activated human and hamster thrombin receptors are mitogenic for the Chinese hamster fibroblast cell line, CCL39. Hirudin and hirugen block the mitogenic effects of thrombin but not the activity of the agonist peptides. Pertussis toxin treated cells do not respond to either alpha-thrombin or the agonist peptides. The data support the idea that the thrombin receptor on CCL39 cells, which is homologous to the thrombin receptor on human platelets, is capable of transmitting mitogenic signals by a mechanism consistent with the tethered ligand hypothesis.
Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486.
C F
CF
Reilly
T M
TM
Connolly
D M
DM
Feng
R F
RF
Nutt
E J
EJ
Mayer
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D015870:Gene Expression; D006629:Hirudins / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008934:Mitogens; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics; D018179:Receptors, Thrombin; D013917:Thrombin / Q000737:chemistry / Q000494:pharmacology*
D006629:Hirudins; D008934:Mitogens; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; C062510:hirugen; D013917:Thrombin