Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis

Atypical protein kinase Cζ (PKCζ) is emerging as a mediator of differentiation. Here, we describe a novel role for PKCζ in myogenic differentiation, demonstrating that PKCζ activity is indispensable for differentiation of both C2C12 and mouse primary myoblasts. PKCζ was found to be associated with a...

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Autores principales: de Thonel, Aurélie, Ferraris, Saima E., Pallari, Hanna-Mari, Imanishi, Susumu Y., Kochin, Vitaly, Hosokawa, Tomohisa, Hisanaga, Shin-ichi, Sahlgren, Cecilia, Eriksson, John E.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854099/
https://www.ncbi.nlm.nih.gov/pubmed/20200223
http://dx.doi.org/10.1091/mbc.E09-10-0847
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author de Thonel, Aurélie
Ferraris, Saima E.
Pallari, Hanna-Mari
Imanishi, Susumu Y.
Kochin, Vitaly
Hosokawa, Tomohisa
Hisanaga, Shin-ichi
Sahlgren, Cecilia
Eriksson, John E.
author_facet de Thonel, Aurélie
Ferraris, Saima E.
Pallari, Hanna-Mari
Imanishi, Susumu Y.
Kochin, Vitaly
Hosokawa, Tomohisa
Hisanaga, Shin-ichi
Sahlgren, Cecilia
Eriksson, John E.
author_sort de Thonel, Aurélie
collection PubMed
description Atypical protein kinase Cζ (PKCζ) is emerging as a mediator of differentiation. Here, we describe a novel role for PKCζ in myogenic differentiation, demonstrating that PKCζ activity is indispensable for differentiation of both C2C12 and mouse primary myoblasts. PKCζ was found to be associated with and to regulate the Cdk5/p35 signaling complex, an essential factor for both neuronal and myogenic differentiation. Inhibition of PKCζ activity prevented both myotube formation and simultaneous reorganization of the nestin intermediate filament cytoskeleton, which is known to be regulated by Cdk5 during myogenesis. p35, the Cdk5 activator, was shown to be a specific phosphorylation target of PKCζ. PKCζ-mediated phosphorylation of Ser-33 on p35 promoted calpain-mediated cleavage of p35 to its more active and stable fragment, p25. Strikingly, both calpain activation and the calpain-mediated cleavage of p35 were shown to be PKCζ-dependent in differentiating myoblasts. Overall, our results identify PKCζ as a controller of myogenic differentiation by its regulation of the phosphorylation-dependent and calpain-mediated p35 cleavage, which is crucial for the amplification of the Cdk5 activity that is required during differentiation.
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spelling pubmed-28540992010-06-30 Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis de Thonel, Aurélie Ferraris, Saima E. Pallari, Hanna-Mari Imanishi, Susumu Y. Kochin, Vitaly Hosokawa, Tomohisa Hisanaga, Shin-ichi Sahlgren, Cecilia Eriksson, John E. Mol Biol Cell Articles Atypical protein kinase Cζ (PKCζ) is emerging as a mediator of differentiation. Here, we describe a novel role for PKCζ in myogenic differentiation, demonstrating that PKCζ activity is indispensable for differentiation of both C2C12 and mouse primary myoblasts. PKCζ was found to be associated with and to regulate the Cdk5/p35 signaling complex, an essential factor for both neuronal and myogenic differentiation. Inhibition of PKCζ activity prevented both myotube formation and simultaneous reorganization of the nestin intermediate filament cytoskeleton, which is known to be regulated by Cdk5 during myogenesis. p35, the Cdk5 activator, was shown to be a specific phosphorylation target of PKCζ. PKCζ-mediated phosphorylation of Ser-33 on p35 promoted calpain-mediated cleavage of p35 to its more active and stable fragment, p25. Strikingly, both calpain activation and the calpain-mediated cleavage of p35 were shown to be PKCζ-dependent in differentiating myoblasts. Overall, our results identify PKCζ as a controller of myogenic differentiation by its regulation of the phosphorylation-dependent and calpain-mediated p35 cleavage, which is crucial for the amplification of the Cdk5 activity that is required during differentiation. The American Society for Cell Biology 2010-04-15 /pmc/articles/PMC2854099/ /pubmed/20200223 http://dx.doi.org/10.1091/mbc.E09-10-0847 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
de Thonel, Aurélie
Ferraris, Saima E.
Pallari, Hanna-Mari
Imanishi, Susumu Y.
Kochin, Vitaly
Hosokawa, Tomohisa
Hisanaga, Shin-ichi
Sahlgren, Cecilia
Eriksson, John E.
Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis
title Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis
title_full Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis
title_fullStr Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis
title_full_unstemmed Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis
title_short Protein Kinase Cζ Regulates Cdk5/p25 Signaling during Myogenesis
title_sort protein kinase cζ regulates cdk5/p25 signaling during myogenesis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854099/
https://www.ncbi.nlm.nih.gov/pubmed/20200223
http://dx.doi.org/10.1091/mbc.E09-10-0847
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