Exploring the Role of cAMP-Dependent Protein Kinase (PKA) Phosphorylation of Rap1b in 'Inside-out' Integrin Activation in Mouse Platelets

Catastrophic cardiovascular events, such as myocardial infarction and ischemic stroke, are mediated by excessive platelet accumulation that results in arterial occlusion. Platelets normally circulate as single cells in an inactive state; however, when exposed to subendothelial matrix proteins or soluble factors such as thrombin, platelets undergo a dramatic process of activation ultimately leading to aggregation of platelets and vessel occlusion. Platelet activation, including shape change, granule release, and integrin activation, occurs through calcium&;The small GTPase, Rap1b, is a PKA substrate and is necessary for normal “&;First, we confirmed previous reports that PGE1 mediates PKA dependent phosphorylation of Rap1b in mouse platelets. PGE1&;Next, we used a Rap1b pull&;Finally, we investigated the effect of Rap1b phosphorylation on &;In summary, we have shown that phosphorylation of Rap1b reduces its membrane association thereby inhibiting Rap1b signaling and consequently preventing &...