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http://purl.uniprot.org/citations/24053798http://www.w3.org/2000/01/rdf-schema#comment"

Background

Differentiation and fusion of skeletal muscle myoblasts into multi-nucleated myotubes is required for neonatal development and regeneration in adult skeletal muscle. Herein, we report novel findings that protein kinase C theta (PKCθ) regulates myoblast differentiation via phosphorylation of insulin receptor substrate-1 and ERK1/2.

Results

In this study, PKCθ knockdown (PKCθshRNA) myotubes had reduced inhibitory insulin receptor substrate-1 ser1095 phosphorylation, enhanced myoblast differentiation and cell fusion, and increased rates of protein synthesis as determined by [3H] phenylalanine incorporation. Phosphorylation of insulin receptor substrate-1 ser632/635 and extracellular signal-regulated kinase1/2 (ERK1/2) was increased in PKCθshRNA cells, with no change in ERK5 phosphorylation, highlighting a PKCθ-regulated myogenic pathway. Inhibition of PI3-kinase prevented cell differentiation and fusion in control cells, which was attenuated in PKCθshRNA cells. Thus, with reduced PKCθ, differentiation and fusion occur in the absence of PI3-kinase activity. Inhibition of the ERK kinase, MEK1/2, impaired differentiation and cell fusion in control cells. Differentiation was preserved in PKCθshRNA cells treated with a MEK1/2 inhibitor, although cell fusion was blunted, indicating PKCθ regulates differentiation via IRS1 and ERK1/2, and this occurs independently of MEK1/2 activation.

Conclusion

Cellular signaling regulating the myogenic program and protein synthesis are complex and intertwined. These studies suggest that PKCθ regulates myogenic and protein synthetic signaling via the modulation of IRS1and ERK1/2 phosphorylation. Myotubes lacking PKCθ had increased rates of protein synthesis and enhanced myotube development despite reduced activation of the canonical anabolic-signaling pathway. Further investigation of PKCθ regulated signaling may reveal important interactions regulating skeletal muscle health in an insulin resistant state."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.org/dc/terms/identifier"doi:10.1186/1471-2121-14-39"xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Dowling A."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Hill J.W."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Marino J.S."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Sanchez E.R."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Hinds T.D. Jr."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"McLoughlin T.J."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Ondrus E."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Onion J.L."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/author"Potter R.A."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/name"BMC Cell Biol"xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/pages"39"xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/title"Suppression of protein kinase C theta contributes to enhanced myogenesis in vitro via IRS1 and ERK1/2 phosphorylation."xsd:string
http://purl.uniprot.org/citations/24053798http://purl.uniprot.org/core/volume"14"xsd:string
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