The mitogen-activated protein kinases (MAPKs) mediate intracellular signals activated by a wide variety of extracellular stimuli [1]. The MAPKs family proteins is composed by: extracellular signal-regulated kinase (ERK)1/2, also known as MAPK, p38 (a/b/g/d), c-Jun amino-terminal kinases (JNK12-13), and ERK5. These serine/threonine kinase are activated by MEK 1/2, MEK3/6, MEK4/7 and MEK5, respectively (Fig. 1) [2]. The RAS-RAF-MEK1/2 pathway is commonly activated by various extracellular stimuli, growth factors, hormones, cytokines and environmental stresses, leading to distinct intracellular responses via either a series of phosphorylation events and of protein-protein interactions involving RAS, RAF, ERK and MEK [1–5].
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