Gsk3β inhibition or cGMP restored the aggregation of PDK1-deficient platelets in response to thrombin, but Gsk3β inhibition diminished the extent of platelet aggregation caused by ADP. (A) A 10-μM final concentration of the Gsk3β inhibitor SB216763 restored full aggregation of PDK1-deficient platelets in response to 0.05 U/mL of thrombin. (B) SB216763 (10 μM) totally inhibited PDK1f/f platelet aggregation but only partially inhibited PDK1−/− platelet aggregation in response to 20 μM ADP. Therefore, Gsk3β plays a more complicated role in ADP-induced platelet activation. (C) Cyclic GMP analog 8-bromo-cGMP (8-Br-cGMP; 1 μM) partially restored the aggregation of PDK1-deficient platelets induced by 0.05 U/mL thrombin. These results suggested that NO/cGMP pathway also plays an important role in PDK1-mediated platelet activation.
