Phosphorylation of rap1B by protein kinase A is not involved in platelet inhibition by cyclic AMP.
The functional consequence of cyclic AMP-dependent phosphorylation of rap1B for stimulus-induced platelet activation is not known. Platelets were pretreated with the stable prostacyclin-analogue iloprost and resuspended in plasma without iloprost. Western blot analysis showed that rap1B was completely converted into its phosphorylated form in the iloprost-pretreated platelets. Surprisingly, the platelets that contained phosphorylated rap1B were found to respond fully to activation by a wide variety of stimuli: aggregation upon stimulation by collagen, phorbol ester, vasopressin, ADP, epinephrine, and ATP-secretion from dense granules induced by collagen, thrombin-receptor activating peptide, vasopressin and phorbol ester were unchanged as compared to control. The results indicate that cyclic AMP-dependent phosphorylation of rap1B does not play a role in the inhibition of the various signal transduction pathways that lead to platelet aggregation and dense granule secretion.
Siess
W
W
Institut für Prophylaxe und Epidemiologie, Universität München, F.R.G.
Grünberg
B
B
D000244:Adenosine Diphosphate / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014667:Vasopressins / Q000494:pharmacology; D020761:rab1 GTP-Binding Proteins
D010703:Phorbol Esters; D010975:Platelet Aggregation Inhibitors; D014667:Vasopressins; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D011494:Protein Kinases; D019204:GTP-Binding Proteins; C061569:RAB1B protein, rat; D020761:rab1 GTP-Binding Proteins; D016285:Iloprost; D004837:Epinephrine