Casein kinase 1α interacts with RIP1 and regulates NF-κB activation

Tumor necrosis factor alpha(TNF alpha) triggers a signaling pathway converging on the activation of NF-kappa B, which forms the basis for many physiological and pathological processes. In a kinase gene screen using a NF-kappa B reporter, we observed that overexpression of casein kinase 1 alpha (CK1 alpha) enhanced TNF alpha-Linduced NF-kappa B activation, and a CK1 alpha kinase dead mutant, CK1 alpha (K46A), reduced NF-kappa B activation induced by TNF alpha. We subsequently demonstrated that CK1 alpha interacted with receptor interacting protein 1 (RIP1) but not with TRADD, TRAF2, MEKK3, MEKK alpha, IKKP beta, or IKK gamma in mammalian cells. RIP1 is an indispensable molecule in TNF alpha/NF-kappa B signaling. We demonstrated that CK1 alpha interacted with and phosphorylated RIP1 at the intermediate domain. Finally, we showed that CK1 alpha enhanced RIP1-mediated NF-kappa B activation. Taken together, our studies suggest that CK1 alpha is another kinase that regulates RIPI function in NF-kappa B activation.