Mitogen-activated protein kinase pathway is involved in the differentiation of muscle cells.

The Journal of Biological Chemistry
E GredingerE Bengal

Abstract

The differentiation of muscle cells is controlled by the MyoD family of transcription factors. This family is regulated by extracellular growth factors that transmit largely unknown signals into the cells. Here we show that the activity of extracellular signal-regulated protein kinase (ERK), a kinase that is part of the mitogen-activated protein kinase (MAPK) cascade, is low in myoblasts and is induced with the onset of terminal differentiation of C2 cells. ERK activity is also induced in fibroblasts that were modified to express MyoD, but not in the parental fibroblast cells. Thus, ERK induction is an intrinsic property of muscle cells. A specific MAPK kinase inhibitor (PD098059) that was added to C2 cells partially inhibited the fusion of myoblasts to multinucleated myotubes without affecting the expression of muscle-specific markers. This inhibitor blocked the induction of MyoD expression that normally takes place during terminal differentiation. Two lines of evidence suggest that the MAPK cascade induces the activity of MyoD: 1) the expression of constitutively activated forms of MEK1 or Raf1 enhanced the transcriptional activity of MyoD in 10T1/2 fibroblasts; and 2) the addition of PD098059 to fibroblast cells expressing a...Continue Reading

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