Erbstatin blocks platelet activating factor-induced protein-tyrosine phosphorylation, polyphosphoinositide hydrolysis, protein kinase C activation, serotonin secretion and aggregation of rabbit platelets.
The role of protein-tyrosine phosphorylation in the signal transduction of platelet activating factor (PAF) was investigated in rabbit platelets with a range of synthetic compounds that inhibit protein-tyrosine kinases. In particular, erbstatin (IC50 approximately 20 micrograms/ml) abrogated a wide range of platelet responses to PAF, including tyrosine phosphorylation of cellular proteins, polyphosphoinositide turnover, activation of membranous protein kinase C, platelet aggregation, and serotonin secretion. With about a third of the potency of erbstatin, compound RG50864 also inhibited many of these responses, whereas at 100 micrograms/ml, genistein, 670C88 and ST271 were without effect. Finally, the ability of thrombin to cause platelet aggregation and serotonin secretion was also compromised by erbstatin.
Salari
H
H
Department of Medicine, University of British Columbia, Vancouver, Canada, UK.
Duronio
V
V
Howard
S L
SL
Demos
M
M
Jones
K
K
Reany
A
A
Hudson
A T
AT
Pelech
S L
SL
D000818:Animals; D000906:Antibodies; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D006868:Hydrolysis; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood*; D010766:Phosphorylation; D019000:Phosphotyrosine; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000097:blood*; D011817:Rabbits; D012701:Serotonin / Q000097:blood*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000906:Antibodies; D006873:Hydroquinones; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D019000:Phosphotyrosine; D012701:Serotonin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C048212:erbstatin