@phdthesis{Dinev2001, author = {Dinev, Dragomir}, title = {Analysis of the role of extracellular signal regulated kinase (ERK5) in the differentiation of muscle cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1180481}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2001}, abstract = {The MEK5/ ERK5 kinase module is a relatively new discovered mitogen-activated protein kinase (MAPK) signalling pathway with a poorly defined physiological function. Since ERK5 and its upstream activator MEK5 are abundant in skeletal muscle a function of the cascade during muscle differentiation was examined. ERK5 becomes activated upon induction of differentiation in mouse myoblasts. The selective activation of the pathway results in promoter activation of differentiation-specific genes, such as the cdk-inhibitor p21 gene, the myosin light chain (MLC1A) gene, or an E-box containing promoter element, where myogenic basic-helix-loop-helix proteins such as MyoD or myogenin bind. Moreover, myogenic differentiation is completely blocked, when ERK5 expression is inhibited by antisense RNA. The effect can be detected also on the expression level of myogenic determination and differentiation markers such as p21, MyoD and myogenin. Another new finding is that stable expression of ERK5 in C2C12 leads to differentiation like phenotype and to increased p21 expression levels under growth conditions. These results provide first evidence that the MEK5/ERK5 MAP kinase cascade is critical for early steps of muscle cell differentiation.}, subject = {Muskelzelle}, language = {en} }