Fig. 7. Scheme for the role of POSH as a scaffold for a multiprotein complex that induces phosphorylation of c-Jun and neuronal apoptosis. Apoptotic stimuli such as NGF deprivation promote the formation of a complex of POSH with GTP-Rac1 as well as with downstream members of the JNK cascade. Association leads to autoactivation of MLKs, which in turn phosphorylate and activate MKK4/7, which in turn phosphorylate and activate JNKs. Association of MKK4/7 and JNKs with POSH may be mediated by an additional member of the complex, designated here as ‘X’. The activated JNKs then phosphorylate and activate c-Jun, which triggers subsequent release of cytochrome c, caspase activation and death.