MAPK14 Human

Mitogen-Activated Protein Kinase 14 (MAPK14), also known as p38-α, is a crucial enzyme in humans encoded by the MAPK14 gene . This kinase is a member of the MAP kinase family, which plays a pivotal role in integrating multiple biochemical signals and is involved in various cellular processes such as proliferation, differentiation, transcription regulation, and development .

MAPK14 is a 41 kDa protein composed of 360 amino acids . It is the prototypic member of the p38 MAPK family, which includes three additional members: MAPK11, MAPK12, and MAPK13, encoding p38β, p38γ, and p38δ MAPK isoforms, respectively .

MAPK14 is activated by various environmental stresses and proinflammatory cytokines . The activation process requires its phosphorylation by MAP kinase kinases (MKKs) or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase . The substrates of MAPK14 include transcription regulators such as ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53 . These substrates suggest the roles of MAPK14 in stress-related transcription, cell cycle regulation, and genotoxic stress response .

MAPK14 is implicated in diverse cellular functions, from gene expression to programmed cell death through a network of signaling molecules and transcription factors . It is mainly activated through MAPK kinase kinase cascades and exerts its biological function via downstream substrate phosphorylation . The kinase is involved in signaling pathways triggered by a variety of stimuli such as growth factors, oxidative stress, UV, cytokines, and DNA damage .

Pharmacological and genetic inhibition of MAPK14 has revealed its biological significance in physiological functions and its potential as a target in human diseases such as immune disorders and heart failure . Diseases associated with MAPK14 include Chlamydia and Spotted Fever .