Cloned platelet thrombin receptor is necessary for thrombin-induced platelet activation.
Platelet activation by thrombin is critical for hemostasis and thrombosis. Structure-function studies with a recently cloned platelet thrombin receptor suggest that a hirudin-like domain in the receptor's extracellular amino terminal extension is a thrombin-binding determinant important for receptor activation. We now report that a peptide antiserum to this domain is a potent and specific antagonist of thrombin-induced platelet activation. This study demonstrates that the cloned platelet thrombin receptor is necessary for platelet activation by thrombin, and provides a strategy for developing blocking monoclonal antibodies of potential therapeutic value.
Hung
D T
DT
Department of Laboratory Medicine, University of California, San Francisco 94143.
Vu
T K
TK
Wheaton
V I
VI
Ishii
K
K
Coughlin
S R
SR
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006629:Hirudins; D006801:Humans; D008969:Molecular Sequence Data; D015539:Platelet Activation / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000502:physiology*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000494:pharmacology*; D014982:Xenopus laevis
D006629:Hirudins; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D013917:Thrombin