Figure 5.

Crosstalk between Raf-dependent, positively regulated signal cascades and a PP2A-dependent negative signaling pathway in cerebral ischemia and reperfusion. In response to ischemia-induced increases in intracellular Ca²⁺, active Src kinase up-regulated ERK cascades through increment of Raf-1 phosphorylation at its active site (Tyr340/341). Meanwhile, Src kinase also contributes to ERK activation through increment of PP2A phosphorylation at its inactivation site (Tyr307) in cerebral ischemia. These two converse signaling pathways undergo crosstalk through ERK and play important roles in ERK/CREB and ERα cascades following cerebral ischemia.