Mitogen-activated protein kinase 7 (MAPK7)

Mitogen-activated protein kinase 7 (MAPK7), commonly known as ERK5 or BMK1, is a serine/threonine kinase belonging to the MAPK family. MAPK7 is distinguished by its large C-terminal regulatory domain, which confers unique auto-inhibitory and transcriptional capabilities. Activated via specific phosphorylation by MEK5, MAPK7 integrates mitogenic and stress signals from cell surface receptors, translocates to the nucleus, and regulates gene expression by phosphorylating various transcription factors, especially AP1 complex members, MEF2C/D, c-Fos, and others. MAPK7 plays vital roles in cell proliferation, survival, differentiation, and is critical for cardiovascular development, vascular integrity, and wound healing. In cancer, MAPK7 is upregulated, promotes tumor cell survival, proliferation, and can confer resistance to apoptosis. Several selective inhibitors and PROTAC degraders have been developed for experimental and potential therapeutic use, but few are clinically approved due to selectivity and safety concerns. Biomarkers include phosphorylated MAPK7 and pathway gene signatures, with applications in oncology and vascular disease research.

Other names

ERK5BMK1 (Big MAP kinase 1)Big MAP kinase 1Extracellular signal-regulated kinase 5MAP kinase 7PRKM7BMK-1BMK1 kinase

ATP-competitive inhibition (most small-molecule inhibitors compete with ATP binding site to block kinase activity). PROTAC-mediated degradation (selective targeting of MAPK7 for ubiquitin-proteasome degradation). Transcriptional activity inhibition (blocking nuclear translocation and transcription factor phosphorylation such as AP1).