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Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by
1Department of Cell Biology, Amgen, Inc., Thousand Oaks, California 91320, USA. Mickey_Hu_99@yahoo.com
Abstract:
The p38 mitogen-activated protein kinases (MAPK) play a crucial role in stress and inflammatory responses and are also involved in activation of the human immunodeficiency virus gene expression. We have isolated the murine cDNA 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 the 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 expanded to many specific tissues in the 12.5-day embryo. At 15.5 days, p38-delta was expressed virtually in most developing epithelia in embryos, suggesting 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, suggesting that p38-delta is a unique stress-responsive protein kinase.
Insights
p38-delta mitogen-activated protein kinase (MAPK) is a stress-responsive kinase. Its expression is developmentally regulated, appearing in adult tissues like the lung and kidney, and in embryonic epithelia, suggesting a key role in development.
Area of Science:
- Molecular Biology
- Cell Signaling
- Genetics
Background:
- p38 mitogen-activated protein kinases (MAPKs) are critical regulators of cellular responses to stress and inflammation.
- MAPKs, including p38, are implicated in human immunodeficiency virus gene expression.
- Understanding the specific roles of p38 MAPK family members is essential for deciphering complex cellular processes.
Purpose of the Study:
- To isolate and characterize murine cDNA clones encoding p38-delta MAPK.
- To determine the chromosomal localization of the p38-delta gene in mice and humans.
- To investigate the expression patterns of p38-delta in adult mouse tissues and embryonic development.
Main Methods:
- Isolation of murine cDNA clones for p38-delta MAPK.
- Gene localization using genetic mapping techniques.
- Expression analysis via Northern hybridization and in situ hybridization.
Main Results:
- p38-delta gene mapped to mouse chromosome 17A3-B and human chromosome 6p21.3.
- Adult p38-delta expression observed primarily in lung, testis, kidney, and gut epithelium.
- Embryonic expression showed developmental regulation, starting in the gut and expanding to most epithelia by day 15.5.
- p38-delta demonstrated distinct substrate specificity compared to p38-alpha.
- p38-delta activation by stress and specific MAPK kinases confirmed its role as a stress-responsive kinase.
Conclusions:
- p38-delta is a developmentally regulated MAPK with distinct characteristics.
- Its expression pattern suggests involvement in epithelial development and function.
- p38-delta represents a unique stress-responsive protein kinase with potential implications in inflammatory and viral processes.