MEK2

MEK2 (mitogen-activated protein kinase kinase 2) is a dual-specificity kinase that activates ERK1/2, regulating DNA repair, proliferation, and differentiation in mammalian cells^[1][2]. Mechanistically, MEK2 interacts with the ribonucleotide reductase subunit p53R2, enhancing RNR activity under serum stimulation and after ionizing radiation, which supports nucleotide supply for DNA synthesis and repair^[2]. Compared with MEK1, MEK2 can be sufficient for the proliferation of specific cancer cells, such as SK-MEL-28 melanoma cells, even when MEK1 activity is inhibited, indicating isoform-specific control of ERK-mediated proliferation^[3]. In disease models, MEK2 knockdown selectively reduces invasive capacity in pancreatic cancer cells, highlighting its distinct contribution to tumor progression^[4]. Inhibition of MEK2 also modulates TREM2 cell surface recruitment in microglia, linking MEK2 signaling to potential neuroinflammatory processes^[5]. Pharmacological inhibitors targeting MEK2, either alone or in combination with MEK1 inhibitors, are being utilized in experimental applications for cancer and inflammatory models, demonstrating the utility of isoform-selective modulation^[6][7][8]. Overall, MEK2 functions as a key regulator within the ERK/MAPK cascade, with specific roles in DNA repair, cellular proliferation, tumor invasiveness, and immune modulation, distinct from the overlapping but non-redundant activities of MEK1^[4][2][3][7].