p38 MAP Kinase (MAPK) participates in a signaling cascade controlling cellular responses to cytokines and stress.There are four p38 MAP kinases in mammals: p38-α (MAPK14), -β (MAPK11), -γ (MAPK12 / ERK6), and -δ(MAPK13/SAPK4), have been identified. Similar to the SAPK/JNK pathway, p38 MAP kinase is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharides (LPS), Ultraviolet light, and growth factors.
In addition, oxidative stress and GPCR stimulation indirectly activate p38. p38 MAPKs regulate downstream targets including several kinases, transcription factors and cytosolic proteins. These kinases include MAPKAPK2, MAPKAPK3, PRAK, MSK1 and MNK 1/2. Some important transcription factors phosphorylated by p38 include tumor suppressor protein p53, CHOP (C/EBP-Homologous Protein), STAT1 (Signal Transducers and Activators of Transcription-1), CREB (cAMP Response Element-Binding Protein), and Max/Myc complexes, etc. The p38 MAPK pathway is a key regulator of pro-inflammatory cytokines biosynthesis at the transcriptional and translational levels, which makes different components of this pathway potential targets for the treatment of autoimmune and inflammatory diseases.