The p38alpha/beta mitogen activated protein kinases act as a molecular switch to regulate satellite cell function

Satellite cells are maintained in a quiescent state until they are activated for maintenance or repair of skeletal muscle tissue. Little is known regarding the mechanisms that maintain this quiescent state or mediate activation. However, the HGF receptor c-met and the FGF receptors 1 and 4 appear to be involved in satellite cell activation and proliferation. Receptor tyrosine kinases are known to signal via MAPKs (mitogen activated protein kinases), and thus MAPKs may help regulate satellite cell activation. MAPKs are organized in signaling cascades including at least two upstream kinases, allowing rapid and specific regulation to elicit cellular responses. The p38alpha/beta MAPKs are activated immediately following muscle damage, and are required for satellite cell activation and proliferation. The p38alpha/beta MAPKs are also required for differentiation of muscle cell lines and for adult satellite cells. Atypical PKClambda regulates p38alpha/beta activity to promote differentiation. These data suggest that p38alpha/beta MAPKs function to activate the quiescent satellite cell, and to mediate the decision to proliferate or differentiate. Under proliferating or differentiating conditions the p38alpha/beta MAPKs phosphorylate distinct substrates, further suggesting these kinases perform distinct roles dependent on cell fate. p38alpha/beta MAPK activity is tightly regulated and MKP-1 negatively regulates p38alpha/beta MAPKs activity in vivo. Analyses of MKP-1-/- satellite cells is consistent with this hypothesis and demonstrates that p38alpha/beta MAPKs plays an essential role in satellite cell function, acting as an intracellular molecular switch to regulate satellite cell activation, proliferation and differentiation.