IKKϵ inhibits PKC to promote Fascin-dependent actin bundling.

Signaling molecules have pleiotropic functions and are activated by various extracellular stimuli. Protein kinase C (PKC) is activated by diverse receptors, and its dysregulation is associated with diseases including cancer. However, how the undesired activation of PKC is prevented during development remains poorly understood. We have previously shown that a protein kinase, IKK epsilon, is active at the growing bristle tip and regulates actin bundle organization during Drosophila bristle morphogenesis. Here, we demonstrate that IKK epsilon regulates the actin bundle localization of a dynamic actin cross-linker, Fascin. IKK epsilon inhibits PKC, thereby protecting Fascin from inhibitory phosphorylation. Excess PKC activation is responsible for the actin bundle defects in IKK epsilon-deficient bristles, whereas PKC is dispensable for bristle morphogenesis in wild-type bristles, indicating that PKC is repressed by IKK epsilon in wild-type bristle cells. These results suggest that IKK epsilon prevents excess activation of PKC during bristle morphogenesis.