Casein kinase 1alpha interacts with RIP1 and regulates NF-kappaB activation

Biochemistry. 2008 Jan 8;47(1):441-8. doi: 10.1021/bi7010515. Epub 2007 Dec 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Casein Kinase I / genetics
  • Casein Kinase I / metabolism*
  • Cell Line
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Binding / drug effects
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • AGFG1 protein, human
  • NF-kappa B
  • Nuclear Pore Complex Proteins
  • RNA-Binding Proteins
  • Tumor Necrosis Factor-alpha
  • Casein Kinase I