J Biol Chem. 2002 Aug 2;277(31):28010-8. Epub 2002 May 28.

Identification of interleukin 1 receptor-associated kinase as a conserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B.External

Mamidipudi, V., Li, X., Wooten, M. W.,
--- - Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA.
The neurotrophin nerve growth factor (NGF) supports neuronal survival by activating the transcription factor nuclear factor-kappaB (NF-kappaB). We report here, for the first time, the identification of p75-associated kinase that mediates NGF-driven NF-kappaB activation. Using co-immunoprecipitation, we demonstrate an NGF-dependent association of interleukin 1 receptor-associated kinase (IRAK) with the p75 neurotrophin receptor in PC12 cells. Our results reveal that IRAK is recruited to the p75-NGF receptor leading to formation of a complex between IRAK, atypical protein kinase C interacting protein, p62, and TRAF6. Activation of NF-kappaB occurs predominantly through the p75 receptor, and TrkA activity suppresses NF-kappaB activation and retards IkappaBbeta degradation. In addition, we observe a requirement for the kinase activity of IRAK in mediating NGF-induced NF-kappaB activation, recruitment of the adapter protein p62 to the p75 receptor, and cell survival. Moreover, p75-IRAK-mediated kappaB activation and the recruitment of IKKbeta, but not IKKalpha, to the receptor require p62. Altogether, our data provide novel information regarding the proximal components involved in p75 receptor signaling and underscore the importance of the atypical PKC interacting protein p62 in this process.
PMID: 12034707External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD IRAK1 Link Myd88 Co-immunoprecipitation PC12 12034707
DD IRAK1 Link NGFR Co-immunoprecipitation PC12 12034707
DD Myd88 Link NGFR Co-immunoprecipitation PC12 12034707
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DD IRAK1 Link NGFR Luciferase assay NF-kB activation 12034707
(Link: click this icon to show interactions only between the two corresponding DDs)