Dual specificity mitogen-activated protein kinase kinase 3 (MKK3) (MKK3)

Dual specificity mitogen-activated protein kinase kinase 3 (MKK3) is a member of the MAP kinase kinase family and is a key activator of the p38 MAPK signaling pathway (UniProt: P46734). It is activated by various environmental stresses and pro-inflammatory cytokines, subsequently phosphorylating p38 at specific threonine and tyrosine residues (NCBI Gene: 5606). This signaling axis is vital for the production of inflammatory cytokines such as TNF-alpha and IL-6, making MKK3 a target of interest for treating chronic inflammatory diseases and certain malignancies (PubMed: 25665524). In cancer, MKK3 has been implicated in tumor progression and survival, although its role can be context-dependent (PubMed: 30212494). Therapeutic strategies targeting MKK3 aim to disrupt the stress-activated protein kinase signaling to reduce inflammation and inhibit pathological cell proliferation. While many clinical efforts have focused on downstream p38 inhibitors, targeting MKK3 offers a potential strategy to modulate the pathway with potentially different selectivity profiles.

Other names

MAP2K3Mitogen-activated protein kinase kinase 3MAP kinase kinase 3MEK3MAPK/ERK kinase 3

Inhibition of the phosphorylation and subsequent activation of p38 mitogen-activated protein kinases (MAPKs) by binding to the ATP-binding site or allosteric sites of MKK3 (UniProt: P46734).