Figure 2.

MLCK activation in endothelial hyperpermeability. Endothelial MLCK is activated in response to multiple cell signalling events including elevated intracellular Ca⁺⁺, protein kinase C (PKC) activation, and signalling through nitric oxide synthase (NOS)- dependent production of NO, and guanylate cyclase (GC)-dependent production of cGMP. Activation of cGMP-dependent protein kinase (PKG) activates MLCK through activation of MEK1 and ERK1/2. Possible direct activation by PKC, PKG, or ERK1/2 is represented by question marks.