p38 is a 38 kDa Stress Activated Protein Kinase/Map Kinase (SAPK/MAPK) that is fully activated by dual phosphorylation on threonine 180 and tyrosine 182, within the activation loop. p38 MAPK plays a critical role in the initiation of G2 delay after ultraviolet radiation; gene knock out studies have also revealed a critical role for p38 in cardiac remodeling. Downstream targets of p38 include the transcription factors ELK1 and ATF2 and the kinases MAPKAPK2 and MAPKAPK5. p38 MAPK plays a role in the production of IL6 and is thought to stabilize erythropoietin production during hypoxic stress. It is activated by environmental stress, many proinflammatory cytokines and lipopolysaccharide. Dual phosphorylation by MAP2K3 and MAP2K6 is required for activation of p38 MAPK. It interacts with MAX, Cdc25B, Cdc25C and binds to the kinase interaction domain in the protein tyrosine phosphatase PTPRR; this interaction retains p38 MAPK in the cytoplasm.