Affiliations: 1) University of Barcelona; 2) Institute of Biomedicine of the University of Barcelona (IBUB)
Keywords: k. regeneration; h. other (signalling pathways responding to stress)
Regeneration is the ability to rebuild a body part that has been damaged or amputated. Drosophila imaginal discs are able to undergo wound healing and regenerative growth after injury or genetic ablation. Reactive oxygen species (ROS) act as early signals that are sensed by the MAP3 kinase Ask1, which in turn activates downstream by phosphorylation the MAP kinases p38 and JNK. Apoptosis can occur as the result of sustained or high activation of these kinases, whereas short or low activation can promote regeneration. In search for the conditions that cells require to activate Ask1-dependent regeneration program we find that PI3K/Akt signaling is necessary for Ask1 to activate p38, but not JNK. In addition, nutrient restriction or mutations that target Ser83 of the Drosophila Ask1 protein, a PI3K/Akt-sensitive residue, impairs regeneration. However, these effects can be reversed by the ectopic activation of p38, but not of JNK. Our results demonstrate that the phosphorylation of p38 during regeneration is nutrient sensitive, and that Ask1 controls the activation of p38 through Ser83. This mechanism is important for discriminating between p38 and JNK signaling pathways in the cells involved in tissue repair and regenerative growth.