Structure and function of platelet membrane glycoproteins Ib and V. Effects of leukocyte elastase and other proteases on platelets response to von Willebrand factor and thrombin.
Treatment of platelets with human leukocyte elastase causes a rapid loss in response to von Willebrand factor and a biphasic loss in response to thrombin, first rapid then more slowly. The rapid phase corresponds to cleavage of a 45-kDa glycopeptide from the extracellular end of membrane glycoprotein GPIb. Longer treatment removes 80-kDa and 90-kDa glycopeptides and a glycopeptide corresponding to the major part of GPV. The 45-kDa and 90-kDa species could be obtained by elastase treatment of glycocalicin, the major proteolytic cleavage product of GPIb. Polyclonal rabbit antibodies against the purified 45-kDa glycopeptide had the same effect on the action of von Willebrand factor and thrombin on platelets as cleavage of GPIb by elastase. These results indicate that both the von Willebrand factor and thrombin binding sites on GPIb are located in the same region on the outside of the molecule. Thrombin activation of platelets involves at least two receptors, one on the 45-kDa glycopeptide, which when occupied causes an increase in the speed of response of the platelets to the cleavage of the second. GPV, a candidate for the second receptor, is a hydrophobic glycoprotein that is cleaved from the platelet membrane by several proteases. Proteases that do not activate platelets but degrade the second receptor remove larger fragments from GPV than do proteases such as thrombin or trypsin which activate platelets.
Wicki
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Clemetson
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KJ
D001792:Blood Platelets / Q000378:metabolism*; D001797:Blood Protein Electrophoresis; D055598:Chemical Phenomena; D002621:Chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007123:Immunoelectrophoresis, Two-Dimensional; D007962:Leukocytes / Q000201:enzymology; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010196:Pancreatic Elastase; D010446:Peptide Fragments / Q000302:isolation & purification; D010447:Peptide Hydrolases; D010779:Photofluorography; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D013917:Thrombin / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D006023:Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C023592:glycocalicin; D014841:von Willebrand Factor; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D013917:Thrombin