Die Proteinkinase D2 als kritischer Parameter während der Skelettmuskeldifferenzierung

Abstract

The developement of every multicellular organism occurs through the highly conserved mechanism of genetic programs orchestrated by genes that coordinate cell growth, proliferation, differentiation, migration and apoptosis. This is regulated by signal transduction cascades mediated by kinases such as protein kinases or phospholipases. Muscle cell differentiation is regulated by the activation of a defined pattern of myogenic transcription factors involving members of the protein kinase C (PKC), Protein kinase D (PKD) or phospholipase D families. The protein kinase D (PKD) isoenzymes PKD1, -2, and -3 are prominent downstream targets of PKCs and PLDs in various biological systems. Recent data suggest that PKDs and PKCs also play an important role in muscle cell differentiation. Hence the influence of PKDs and PKCs was examined by establishing the model of C2C12 cells as a known in vitro model for muscle cell differentiation. PKD expression could be demonstrated in C2C12 cells with PKD2 being highly expressed. Furthermore the activation of PKD2 at the beginning of muscle cell differentiation could be observed and inihibited by using pharmacological inhibitors. Depletion of PKD2 by shRNA resulted in a marked inhibition of satellite cell fusion. Furthermore, an activation of myocyte enhancer factor 2D, a key transcription factor for muscle cell differentiation in satellite cells by PKD2 could be observed. In conclusion, the PKD family, especially PKD2 can be seen as a major mediator of muscle cell differentiation in vitro and thereby as a potential novel target for the modulation of muscle regeneration.