Calpains are involved in phosphatidylinositol 3',4'-bisphosphate synthesis dependent on the alpha IIb beta 3 integrin engagement in thrombin-stimulated platelets.
In thrombin-stimulated platelets alpha IIb beta 3 integrin engagement triggers both phosphatidylinositol 3',4'-bisphosphate synthesis and calpain activation. We checked the possible involvement of calpains in phosphatidylinositol 3-kinase signalling pathway using a cell permeant specific inhibitor of calpains, calpeptin. In conditions where thrombin-induced platelet aggregation and secretion were not impaired, we found a dose-dependent inhibition of phosphatidylinositol 3,4-bisphosphate synthesis by calpeptin from 50 micrograms/ml. Moreover, pretreatment of platelets by both calpeptin and the peptide RGDS, an inhibitor of fibrinogen binding to activated alpha IIb beta 3 integrin, did not induce additive effects on phosphatidylinositol 3,4-bisphosphate inhibition. Finally, the p85 regulatory subunit of phosphatidylinositol 3-kinase was still translocated to the cytoskeleton in calpeptin-treated platelets. These data indicate that calpains are involved in the regulation of alpha IIb beta 3 integrin-dependent phosphatidylinositol 3-kinase signalling pathway.
Montsarrat
N
N
Institut Fédératif de Recherche en Immunologie Cellulaire et Moléculaire, INSERM, Unité 326, Hôpital Purpan, Toulouse, France.
Racaud-Sultan
C
C
Mauco
G
G
Plantavid
M
M
Payrastre
B
B
Breton-Douillon
M
M
Chap
H
H
D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology*
D004151:Dipeptides; D016023:Integrins; D018129:Phosphatidylinositol Phosphates; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C060980:phosphatidylinositol 3,4-diphosphate; C071482:calpeptin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D013917:Thrombin; D002154:Calpain