THE ROLE OF P38 MAPK PHOSPHORYLATION IN AGING
Aging affects most organisms on our planet and is a factor in many diseases, yet we still do not fully understand the factors involved. Our lab developed a model of aging by manipulating the p38 MAPK (p38Kb) gene in Drosophila melanogaster (fruit fly). Over-expression of p38Kb results in a 37% lifespan extension whereas loss of p38Kb results in a reduced lifespan. The activation of p38Kb is regulated by its dual phosphorylation on the threonine and tyrosine of the TGY motif. We are interested in how p38Kb phosphorylation contributes to lifespan and other aging phenotypes. To do this, we are making transgenic flies that are phospho null for p38Kb in which the T and Y are mutated to alanine (p38Kbala2). As alanine cannot be phosphorylated, this substitution makes a form of p38Kb that cannot be phosphorylated. In addition, we are also making flies that are phospho mimic for p38Kb in which the T and Y are mutated to aspartic acid (p28Kbasp). Aspartic acid has a negatively charged side chain that mimics the structure/charge of a phosphorylated threonine or tyrosine. As a result, the protein can behave as though it is phosphorylated even when it is not. Here, we will discuss our cloning strategy for making these transgenic flies. Once we have our mutations in the final vector, we can then observe their effects on lifespan and aging phenotypes such as locomotor functions.
Brewer, Deja, "THE ROLE OF P38 MAPK PHOSPHORYLATION IN AGING" (2019). University Research Symposium. 249.