Mitogen-activated protein kinase kinase 3 (MEK3) (MEK3)

Mitogen-activated protein kinase kinase 3 (MEK3), also known as MAP2K3 or MKK3, is a dual-specificity protein kinase that serves as a critical activator of the p38 MAPK signaling pathway [21, 24]. It is primarily activated by environmental stresses, such as osmotic shock and UV radiation, as well as pro-inflammatory cytokines [21, 28]. Upon activation, MEK3 phosphorylates p38 MAP kinases, which then regulate a wide array of cellular processes including inflammation, cell cycle arrest, and apoptosis [22, 24]. In the context of disease, MEK3 is often dysregulated; its overexpression is linked to inflammatory conditions like rheumatoid arthritis and various malignancies where it can promote tumor cell survival or invasion [21, 32, 36]. Conversely, in some cancers like acute lymphoblastic leukemia, loss-of-function mutations in MEK3 may contribute to aberrant proliferation by inactivating the growth-inhibitory p38 pathway [22]. While most clinical MEK inhibitors target the MEK1/2 isoforms, MEK3 is an emerging therapeutic target for inflammatory diseases and specific cancer subtypes, with several small-molecule inhibitors like Gossypetin and (R)-STU104 currently in preclinical development [21, 31, 33]. Therapeutic challenges include potential off-target effects and systemic toxic}

Other names

MAP2K3MKK3MAPKK3PRKMK3SAPKK2

Inhibition of phosphorylation of p38 MAPK and disruption of upstream kinase interactions [31, 33]