Fig. 2. (A) Some of the mechanisms involved in regulating calpain activity. (B) Possible pathway for growth-factor-induced, calpain-mediated cell migration. Binding of epidermal growth factor (EGF) to its receptor (EGFR) activates a MAP kinase cascade that eventually activates ERK. The scaffolding function of FAK brings ERK and calpain 2 into a complex, resulting in phosphorylation of calpain 2. This ERK-mediated phosphorylation leads to activation of calpain 2, which can be counteracted by phosphorylation of calpain 2 by PKA. Active calpain 2 can then cleave talin 1, leading to adhesion complex turnover and cell migration.