[Retracted] Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems

Figure 2

Effect of activation by arsenate (As(V)) and arsenite (As(III)) on the signal transduction pathways. As(V) and As(III) activate different proteins to regulate c-Jun N-terminal kinase (JNK), which functions in the stress-activated protein kinase pathway (SAPK). A SAPK pathway is a sequential protein kinase cascade where mitogen-activated protein (MAP) kinase kinase kinase kinase (MAP4 K) phosphorylates and activates a MAP kinase kinase kinsase (MAP3 K), which repeats the cycle by phosphorylating and activating the next kinase in the cascade. The small GTP binding proteins (G-proteins: Ras, Rac, Cdc-42, and Rho) are localized upstream of the sequential protein kinase cascade. The anion transport protein regulates entry of arsenate into the cell, while arsenite, which is an uncharged arsenic species, enters the cell by diffusion. The small G-proteins that are regulated by As(V) and As(III) do not appear to play a significant role in As(V) and As(III) signaling to JNK. The p-21-activated kinase (PAK) plays a role in As(III)-dependent JNK activity. MEKK3 and MEKK4 are involved in both As(V) and As(III) activation of JNK, while MEKK2 may be involved in the activation of JNK by As(III) (Porter et al.) [6].