Fig. 3

Potential points of action of flavonoids within ERK pathway. ERK1/2 are activated by upstream MAPKK, such as MEK1/2, and MAPKKK, such as c-Raf. MEK1/2 induce ERK1/2 activation via dual phosphorylation on threonine 202 and tyrosine 204 residues within the tripeptide motif TEY. Phosphorylation of ERK leads to the activation of a number of transcription factors, important in controlling differentiation, neuronal survival and various forms of cellular plasticity. For example, ERK activates pro-survival transcription factor CREB, by activating both p90RSK and MSK1/2. Other important targets include, ATF-1, Elk-1 and stat1/3, all of which are implicated in the regulation of various forms of cellular stress, including genotoxic agents, inflammatory cytokines and UV irradiation