CHARACTERIZING THE BIOCHEMICAL AND BIOLOGICAL EFFECTS OF P38 ISOFORMS IN MYOGENESIS

Abstract

The p38 MAPKs, primarily p38α, have critical roles in various signal transduction pathways that control many cellular and multicellular processes, among these processes myogenesis. The original thesis plan was to knock-out the genes encoding p38 isoforms in the myogenic C2 cell line in order to try and address the role of new phosphorylation site of p38 isofors discovered in vivo in muscle systems. Unexpectedly however, C2 cells knocked-out of each of p38 isoforms and C2p38α/γ-/- double KO were able to differentiate normally. We thus, further established C2p38α/γ/β-/- triple knockout cells and observed that these cells failed to undergo myoblasts-to-myofibers differentiation. Two important conclusions can be drawn from the results of this thesis. One, that the p38α/β axis is critical for the myoblasts-to-myofibers differentiation of C2 cells, but any isoform can support the process. Two, a multilayered cross-talk exists between p38 isoforms in C2 cells. Finally, the set of C2 KO derived cells provides an unequivocal tool for studying the biochemistry and physiological effects of p38 isoforms in myogenesis.