Protein kinase Czeta regulates Cdk5/p25 signaling during myogenesis

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: de Thonel, Ferraris, Pallari, Imanishi, Kochin, Hosokawa, Hisanaga, Sahlgren, Eriksson
Förläggare: American Society for Cell Biology
Publiceringsår: 2010
Tidskrift: Molecular Biology of the Cell
Tidskriftsakronym: Mol Biol Cell
Volym: 21
Nummer: 8
Artikelns första sida, sidnummer: 1423
Artikelns sista sida, sidnummer: 1434
ISSN: 1939-4586
eISSN: 1939-4586


Atypical protein kinase Czeta (PKCzeta) is emerging as a mediator of differentiation. Here, we describe a novel role for PKCzeta in myogenic differentiation, demonstrating that PKCzeta activity is indispensable for differentiation of both C2C12 and mouse primary myoblasts. PKCzeta 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 PKCzeta 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 PKCzeta. PKCzeta-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 PKCzeta-dependent in differentiating myoblasts. Overall, our results identify PKCzeta 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.

Senast uppdaterad 2020-28-01 vid 05:39