The p38 family refers to the SAPK2/3 Kinases (Stess-Activated Protein Kinases), a subfamily of JNK/SAPK family. p38/SAPK Kinases are also activated by stresses, most notably inflammatory cytokines, irradiation, and certain toxins such as anisomycin and arsenite. SAPKs have been implicated in many pathological conditions, including inflammation, cancer and neurodegenerative diseases. As with the other MAPK family members (ERK, JNK, p38MAPK, and ERK5), p38 is activated through phosphorylation on both threonine and tyrosine residues at the Thr-X-Tyr dual phosphorylation motif, where X is Gly for p38. Once phosphorylated and active, it then goes on to phosphorylate downstream targets in both the cytoplasm and the nucleus. Some of their main targets of p38 are the kinase MAPKAPK2 and the transcription factor ATF2 that are activated via their phosphorylation.