We recently isolated a cDNA clone encoding a functional platelet thrombin receptor that defined a unique mechanism of receptor activation. Thrombin cleaves its receptor's extracellular amino terminal extension, unmasking a new amino terminus that functions as a tethered peptide ligand and activates the receptor. A novel peptide mimicking this new amino terminus was a full agonist for platelet secretion and aggregation, suggesting that this unusual mechanism accounts for platelet activation by thrombin. Does this mechanism also mediate thrombin's assorted actions on non-platelet cells? We now report that the novel thrombin receptor agonist peptide reproduces thrombin-induced events (specifically, phosphoinositide hydrolysis and mitogenesis) in CCL-39 hamster lung fibroblasts, a naturally thrombin-responsive cell line. Moreover, these thrombin-induced events could be recapitulated in CV-1 cells, normally poorly responsive to thrombin, after transfection with human platelet thrombin receptor cDNA. Our data show that important thrombin-induced cellular events are mediated by the same unusual mechanism of receptor activation in both platelets and fibroblasts, very likely via the same or very similar receptors.
Article|
February 01 1992
Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor.
D T Hung,
D T Hung
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
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T H Vu,
T H Vu
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
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N A Nelken,
N A Nelken
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
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S R Coughlin
S R Coughlin
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
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D T Hung
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
T H Vu
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
N A Nelken
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
S R Coughlin
Department of Laboratory Medicine, University of California, San Francisco 94143-0524.
Online Issn: 1540-8140
Print Issn: 0021-9525
J Cell Biol (1992) 116 (3): 827–832.
Citation
D T Hung, T H Vu, N A Nelken, S R Coughlin; Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor.. J Cell Biol 1 February 1992; 116 (3): 827–832. doi: https://doi.org/10.1083/jcb.116.3.827
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