Fig. 8: Proposed model for the participation of C3G in platelet signaling.
From: C3G contributes to platelet activation and aggregation by regulating major signaling pathways
C3G participates in the second wave of Rap1 activation induced by thrombin, which leads to its activation by phosphorylation at Tyr504 through the PKC-Src pathway. C3G phosphorylation is also regulated by ERKs and p38 MAPKs: ERKs inhibit the Shp2 tyrosine phosphatase, allowing C3G phosphorylation, and both MAPKs control the production of TXA2. C3G, via Rap1-dependent and -independent mechanisms, regulates TXA2 synthesis through a negative feedback loop involving the inhibition of cPLA2. PLC: phospholipase C; DAG: diacylglycerol; AA: arachidonic acid; TXA2: thromboxane A2; TXA2R: TXA2 receptor; cPLA2: cytosolic phospholipase A2; BIS: bisindolylmaleimide, an inhibitor of PKC; PP2: a Src inhibitor; wortmannin: a PI3K inhibitor; SHP099: a Shp2 inhibitor; U0126: an ERK inhibitor; SB203580: a p38α/β MAPK inhibitor; aspirin: a cyclooxygenase inhibitor. Dashed gray lines indicate a hypothetical Rap1-dependent pathway that could regulate the activation of ERKs and p38 MAPKs.
