Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines

The p38 mitogen-activated protein kinases (MAPK) play a crucial role in str ess and inflammatory responses and are also involved in activation of the h uman immunodeficiency virus gene expression. We have isolated the murine cD NA clones encoding p38-delta MAPK, and we have localized the p38-delta gene to mouse chromosome 17A3-B and human chromosome 6p21.3. By using Northern and in situ hybridization, we have examined the expression of p38-delta in the mouse adult tissues and embryos, p38-delta was expressed primarily in t he lung, testis, kidney, and gut epithelium in the adult tissues. Although p38-delta was expressed predominantly in the developing gut and the septum transversum in the mouse embryo at 9.5 days, its expression began to be exp anded to many specific tissues in the 12.5-day embryo. At 15.5 days, p38-de lta was expressed virtually in most developing epithelia in embryos, sugges ting that p38-delta is a developmentally regulated MAPK. Interestingly, p38 -delta and p38-alpha were similar serine/threonine kinases but differed in substrate specificity. Overall, p38-delta resembles p38-gamma, whereas p38- beta resembles p38-alpha. Moreover, p38-delta is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7, sugge sting that p38-delta is a unique stress-responsive protein kinase.