Subtype specific roles of mitogen activated protein kinases in L6E9 skeletal muscle cell differentiation

Role of mitogen activated protein kinases (MAPK) in skeletal muscle differentiation is not fully understood. We investigated subtype-specific functions and their interactions, if any, in the regulation of myogenic differentiation in L6E9 skeletal muscle cells. We show inhibition of extracellular signal-regulated kinase-1 and -2 (ERK-1/-2) and activation of p38 MAP kinase during the differentiation of L6E9 rat skeletal muscle cells under low serum condition. Inhibition of ERK-1/-2 activity dramatically enhanced differentiation as was evident from cellular morphology, expression of muscle differentiation specific marker proteins, suggesting that ERK-1/-2 activation may be inhibitory to initiation and progression of differentiation. In contrast, inhibition of p38 MAP kinase completely prevented differentiation; meaning p38 activation is required from the initiation till terminal differentiation of L6E9 cells. Moreover, inhibition of ERK-1/-2 activities enhanced the activation of p38 MAP kinase that resulted in enhancement of differentiation; whereas inhibition of p38 MAP kinase activity enhanced the ERK-1/-2 activities culminating in abrogation of differentiation. We conclude that ERK-1/-2 and p38 MAP kinase cascades oppositely regulate each other's function(s) thereby regulating L6E9 skeletal muscle differentiation.