Figure 9.

A tentative model for PKCζ signaling during muscle differentiation. The up-regulation of PKCζ activity during myoblast differentiation promotes the activation of Cdk5 in a calpain-dependent manner. PKCζ phosphorylates the Cdk5 activator protein, p35, and calpains. Consecutively, calpains are activated and trigger the cleavage of the phosphorylated p35 to its more stable fragment, p25, leading to a sustained activation of Cdk5. PKCζ is able to break the autoinhibitory loop, where Cdk5 restrains the p35 processing and p25 generation by phosphorylating p35. Thus, PKCζ is a major upstream regulator of Cdk5 kinase activity essential for the progression of the myogenic differentiation.