... functions of b-arrestins, or by modulating the activity of proteinkinase C, which can activate Raf isoforms at the apex of the ERK1/2 module (reviewed in [42]).Redox regulation at each of these ... 1).GTP-loaded Ras promotes activation of the MAPK kinasekinase Raf-1. Raf-1 then activates the MAPK kinaseMEK1/2, leading to ERK1/2 phosphorylation. In addition,MEK1/2 can be activated by B-Raf, ... phosphatases(PP) as well. Likewise, ubiquitin-proteasome (Ub-P) mediated degra-dation of phospho-ERKs may become impaired. Several of thesemechanisms may coexist, mediating the sustained ERK signalingobserved...