Casein Kinase Iγ2 Impairs Fibroblasts Actin Stress Fibers Formation and Delays Cell Cycle Progression in G1

Figure 13

Model describing how CKIγ2 prevents the formation of actin stress fibers and regulates cell proliferation. Overexpression of CKIγ2 activates Cdk5, which contributes to p27^Kip1 stabilization and cytoplasmic accumulation following phosphorylation of p27^Kip1 at Ser¹⁰. Increased cytoplasmic level of p27^Kip1 correlates with decreased cellular levels of RhoA. p27^Kip1 also inhibits RhoA activation by directly binding to RhoA and competing RhoA interaction with RhoGEFs. Reduced RhoA signaling then results in decreased formation of stress fibers. Roscovitine rescues RhoA activation and signaling by inhibiting CKIγ2-induced activation of Cdk5 therefore prevents p27^Kip1 phosphorylation at Ser¹⁰ and promotes p27^Kip1 degradation. (1) indicates CKIγ2 kinase-independent, while (2) represents CKIγ2 kinase-dependent.