Mitogen-activated protein kinase 14 (MAPK14) (p38α)

Mitogen-activated protein kinase 14 (MAPK14), commonly known as p38α, is a pivotal serine/threonine kinase that integrates signals from various environmental stresses and pro-inflammatory cytokines [10, 11]. It belongs to the p38 MAPK family and is activated by dual phosphorylation on a Thr-Gly-Tyr motif by upstream kinases like MKK3 and MKK6 [10, 12]. Once active, p38α phosphorylates numerous downstream targets, including transcription factors (e.g., ATF2, MEF2C) and other kinases (e.g., MK2), thereby regulating gene expression, cell cycle progression, and apoptosis [11, 12]. In pathological contexts, p38α is a major driver of chronic inflammatory diseases such as rheumatoid arthritis and COPD, and it plays complex roles in cancer as both a tumor suppressor and a promoter of metastasis [1, 2]. Despite the development of many potent small-molecule inhibitors, clinical advancement has been hindered by systemic toxicities, particularly hepatotoxicity and skin reactions [5, 7]. Current research continues to explore its potential in neurodegenerative diseases like Alzheimer's and rare conditions such as facioscapulohumeral muscular dystrophy (FSHD) [3, 5].

Other names

p38SAPK2ACSBPRKMXI2CSAID-binding proteinMAPK14

ATP-competitive inhibition (Type I), Allosteric inhibition (Type II) [6]