Casein kinase 1alpha interacts with RIP1 and regulates NF-kappaB activation.
Tumor necrosis factor alpha (TNFalpha) triggers a signaling pathway converging on the activation of NF-kappaB, which forms the basis for many physiological and pathological processes. In a kinase gene screen using a NF-kappaB reporter, we observed that overexpression of casein kinase 1alpha (CK1alpha) enhanced TNFalpha-induced NF-kappaB activation, and a CK1alpha kinase dead mutant, CK1alpha (K46A), reduced NF-kappaB activation induced by TNFalpha. We subsequently demonstrated that CK1alpha interacted with receptor interacting protein 1 (RIP1) but not with TRADD, TRAF2, MEKK3, IKKalpha, IKKbeta, or IKKgamma in mammalian cells. RIP1 is an indispensable molecule in TNFalpha/NF-kappaB signaling. We demonstrated that CK1alpha interacted with and phosphorylated RIP1 at the intermediate domain. Finally, we showed that CK1alpha enhanced RIP1-mediated NF-kappaB activation. Taken together, our studies suggest that CK1alpha is another kinase that regulates RIP1 function in NF-kappaB activation.
Wang
Yong
Y
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Sun
Xiaoqing
X
Wu
Jun
J
Xu
Bing-e
BE
Gu
Cuiping
C
Wang
Hui
H
Wang
Xin
X
Tan
Fengwei
F
Peng
Xiaozhong
X
Qiang
Boqin
B
Yuan
Jiangang
J
Luo
Ying
Y
D015153:Blotting, Western; D047389:Casein Kinase I / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C119724:AGFG1 protein, human; D016328:NF-kappa B; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D047389:Casein Kinase I