MNK2

MNK2, or MAP kinase-interacting serine/threonine-protein kinase 2, is a protein kinase in humans encoded by the MNK2 gene. It is a member of the MNK family, which includes MNK1, and functions as a downstream effector of the MAP kinase signaling pathways. MNK2 is activated by the mitogen-activated protein kinases ERK1/2 and p38 through direct phosphorylation at regulatory docking sites. Once activated, MNK2 phosphorylates the cap-binding protein eIF4E on serine 209, linking MAPK signaling to the control of translation initiation.

By phosphorylating eIF4E, MNK2 modulates the translation of a subset of mRNAs, often those with structured 5' untranslated regions, influencing cell growth, survival, and stress responses. The enzyme possesses a typical kinase core and regulatory regions that include docking motifs for interaction with MAPKs. Multiple isoforms exist due to alternative splicing, including MNK2a and MNK2b, which differ in regulatory regions and may have distinct activity or localization patterns.

Physiologically, MNK2 participates in regulating protein synthesis in response to growth factors and cellular stress. Its roles may extend to immune and neural processes, with tissue-specific contributions that can vary relative to MNK1. In disease contexts, dysregulation of the MNK/eIF4E axis has been associated with cancer and inflammatory conditions, though the exact contribution of MNK2 versus MNK1 can be context-dependent.

Therapeutically, inhibition of MNK1 and MNK2 to reduce eIF4E phosphorylation is under investigation as a strategy for cancer and inflammatory diseases. Inhibitors such as tomivosertib (eFT-508) target MNK1/2, and other compounds like cercosporamide have been studied as MNK inhibitors in preclinical and clinical settings.