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MNK

The Erk (extracellular regulated kinase) and p38 (mitogen-activated protein kinase) MAPK pathways are known to play important roles in mediating multiple biological processes including development, apoptosis, autophagy, oncogenesis, inflammation, etc. Kinases that can be phosphorylated by multiple MAPKs such as the MAPK interacting protein kinases (Mnks) can exert multiple biological functions due to their ability to respond to a wide range of external stimuli such as mitogens as well as stress inducers. The Mnk kinase family includes Mnk1 and Mnk2 which were originally discovered in two independent screens as substrates for Erk1 and Erk2. It is now well established that the Mnk kinases can be activated by either Erk or p38 MAPKs in response to multiple extracellular stimuli and phosphorylate their major downstream effector, the cap binding eukaryotic initiation factor 4E (eIF4E). Mnk1 and Mnk2 are serine/threonine kinases with substantial similarity in their coding sequences and motifs present in their structures. 
Both kinases contain a N-terminal basic amino acid rich region that can mediate their localization; a catalytic domain similar to the serine/threonine kinases such as the Rsks, Ca21/calmodulin (CaM)-dependent kinases, Mapkap kinase-2 and Mapkap kinase-3 containing conserved MAPK phosphorylation sites; and an MAPK binding domain in their carboxyl terminus. Mnk1 is activated in response to treatment with growth factors, ultraviolet (UV) radiation, mitogens and stress inducing agents such as anisomycin or sorbitol as well as by cytokines such as type I and type II interferons (IFNs), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, etc. In contrast Mnk2 exhibits high basal activity that is more resistant to the inhibition of Erk and p38 and these observations can be partially explained by differences in the C-terminal domains of the Mnk kinases.