Dual specificity mitogen-activated protein kinase kinase 5 (MAP2K5)

Dual specificity mitogen-activated protein kinase kinase 5 (MAP2K5), also known as MEK5, is a dual-specificity protein kinase that belongs to the MAP kinase kinase family. It serves as the sole upstream activator of ERK5 (MAPK7), phosphorylating it on both threonine and tyrosine residues within the TEY activation motif [UniProt: Q13163]. This signaling axis is triggered by various stimuli, including growth factors like EGF and IGF-1, as well as environmental stresses, and is crucial for regulating cell proliferation, survival, and differentiation [PubMed: 16449638]. MAP2K5 is frequently implicated in the pathogenesis of several cancers, where its overexpression is linked to increased tumor aggressiveness, metastasis, and poor prognosis, particularly in prostate and breast cancers [PubMed: 33806357]. Additionally, the MAP2K5-ERK5 pathway plays a significant role in cardiovascular physiology, specifically in cardiac hypertrophy and endothelial cell function [PubMed: 11560854]. While no MAP2K5 inhibitors are currently FDA-approved, research compounds like BIX02189 and SC-1-151 are widely used in preclinical studies to investigate the therapeutic potential of targeting this kinase in oncology and inflammatory diseases [PubChem: 25144451].

Other names

MEK5MKK5MAPKK5PRKMK5MAP kinase kinase 5

Inhibition of the kinase activity of MAP2K5, thereby preventing the phosphorylation and subsequent activation of its downstream substrate, ERK5 (MAPK7).