Mitogen-activated protein kinase 1 and Mitogen-activated protein kinase 14 (MAPK1 and MAPK14)

Mitogen-activated protein kinase 1 (MAPK1/ERK2) and Mitogen-activated protein kinase 14 (MAPK14/p38 alpha) are essential serine/threonine kinases within the MAPK signaling network that regulate critical cellular responses to extracellular stimuli [1, 4]. MAPK1 is a central component of the canonical Ras-Raf-MEK-ERK pathway, which primarily mediates signals from growth factors to drive cell proliferation, survival, and differentiation [11, 14]. In contrast, MAPK14 is the prototypic member of the p38 MAPK family, typically activated by environmental stresses and proinflammatory cytokines to regulate apoptosis and the production of inflammatory mediators like TNF-alpha [1, 6]. Both kinases are significant therapeutic targets; MAPK1 inhibitors are primarily investigated for treating various cancers with MAPK pathway mutations, while MAPK14 inhibitors have been explored for inflammatory diseases such as rheumatoid arthritis and asthma, as well as certain cancers and neurodegenerative disorders [2, 12]. Despite their therapeutic potential, targeting these kinases faces challenges such as dose-limiting toxicities and the complex feedback loops within the signaling network [10, 14]. Understanding the interplay between these two pathways is crucial for developing effective combination therapies and managing potential off-target effects [8, 11].

Other names

ERK2p38 alphaExtracellular signal-regulated kinase 2SAPK2APRKM1PRKM14CSBPp42-MAPKMitogen-activated protein kinase 2Cytokine suppressive anti-inflammatory drug-binding protein

ATP-competitive inhibition of kinase activity, preventing the phosphorylation of downstream substrates in the ERK and p38 MAPK signaling pathways.