The common pathway for alpha- and gamma-thrombin-induced platelet activation is independent of GPIb: a study of Bernard-Soulier platelets.
The responses to alpha- and gamma-thrombin were studied in normal and Bernard-Soulier platelets labelled with [32P]phosphate, to investigate the relationship between thrombin binding to the platelet membrane glycoprotein Ib (GPIb) and thrombin-induced platelet activation. For this purpose we conducted parallel studies of the kinetics of platelet aggregation, granule secretion, hydrolysis of polyphosphoinositides, formation of phosphatidic acid, phosphorylation of the myosin light chain (p20) and of the 43 kDa protein (p43), and thromboxane B2 formation. Like alpha-thrombin, gamma-thrombin activated control platelets via all the above metabolic responses, but only after a prolonged lag. In Bernard-Soulier platelets, alpha-thrombin induced polyphosphoinositide hydrolysis and phosphatidic acid formation, p20 and p43 phosphorylation, thromboxane B2 formation, secretion and to a lesser extent aggregation, but only after a prolonged lag. The metabolic responses of Bernard-Soulier platelets to gamma-thrombin were very similar to those of control platelets. We have previously showed that GPIb which is not present in Bernard-Soulier platelets binds alpha- but not gamma-thrombin. The present results indicate that thrombin binding to GPIb is not directly coupled either with the activation of phospholipase C specific to polyphosphoinositides, or with the activation of protein kinase C and phospholipase A2. However, thrombin binding to GPIb appears to promote an early mechanism which accelerates all the platelet responses.
Jandrot-Perrus
M
M
Laboratoire de Recherche sur l'Hémostase et la Thrombose, Faculté Xavier Bichat, Paris, France.
Rendu
F
F
Caen
J P
JP
Levy-Toledano
S
S
Guillin
M C
MC
D000328:Adult; D001606:Bernard-Soulier Syndrome / Q000097:blood*; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D001798:Blood Proteins; D010716:Phosphatidylinositols; D010980:Platelet Membrane Glycoproteins; D013929:Thromboxane B2; D013917:Thrombin