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...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2010
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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. |
format | Text |
id | pubmed-2854099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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