Skip to main content
Figure 3 | Skeletal Muscle

Figure 3

From: The myogenic kinome: protein kinases critical to mammalian skeletal myogenesis

Figure 3

Regulation of the late myogenic transcriptional program by the kinome. The figure shows the mechanisms by which the kinases described in the text coordinate myoblast cell cycle exit, myoblast differentiation, myocyte fusion and myotube hypertrophy. Cell-cell contact and N-cadherin ligation, in conjunction with transforming growth factor-β-activated kinase 1 (TAK1) and MAP kinase kinase 3/6 (MKK), activate p38α. p38α induces cell cycle exit and differentiation through the phosphorylation of MEF2 and E47 that together with MyoD form part of an active myogenic transcriptional complex. A subunit of this complex is RNA polymerase II (RNA Pol II), which is phosphorylated and activated by cyclin-dependent kinase 9 (CDK9). Akt2, in response to IGF stimulation, phosphorylates the transcriptional coactivator and histone acetyltransferase p300, which is part of the same myogenic transcriptional complex. Activation of the Akt2 pathway promotes differentiation and hypertrophy by several other mechanisms as well. Akt2 phosphorylates and inactivates the FoxO family of transcription factors, whose activities are inhibitory to differentiation and hypertrophy. Phosphorylation of the mammalian target of rapamycin (mTOR) by Akt2 encourages protein synthesis/hypertrophy, partly through mTOR's phosphorylation and activation of the ribosomal protein S6 kinase 1 (S6K). Akt2 can also phosphorylate and inhibit glycogen synthase kinase 3β (GSK3). When active, GSK3 inhibits differentiation and hypertrophy through phosphorylation and cytoplasmic sequestration of NFATC3. Phosphorylation of β-catenin by GSK3 similarly prevents its nuclear accumulation and ability to activate the TCF/LEF family of transcription factors. Finally, activation of extracellular signal-regulated kinase 2 (ERK2) by an unknown stimulus promotes cell fusion through the phosphorylation and nuclear accumulation of NFAT3 via the 90-kDa ribosomal S6 kinase 2 (RSK2).

Back to article page
\