CCM2 as a Scaffold for p38 MAPK Activation. As described in  the Rho-GTPase, RAC, is recruited to actin membrane ruffles by CCM2 following hyperosmotic stress, facilitating the activation of p38 MAPK. CCM2 acts as a scaffold binding to RAC, MAP3K3, and MAP2K3 to organize these components into a functional signaling module. We have included in this model the two additional upstream MAP2Ks to p38 MAPK: MAP2K6, a specific activator of p38 MAPK related to MAP2K3; and MAP2K4, which primarily activates the JNK/SAPK pathway, but can also phosphorylate p38 MAPK in vitro. These two kinases may contribute to activating p38 MAPK in response to hyperosmotic stress but unlikely via interactions with CCM2 . Downstream substrates of p38 MAPK include MAPKAPK2 and MAPKAPK5. Figure adapted from Uhlik et al. .
Fong et al. BMC Developmental Biology 2007 7:2 doi:10.1186/1471-213X-7-2