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Papers In Press, published online ahead of print May 28, 2002
Biological Sciences, Auburn University, Auburn, AL 36849
Corresponding Author: Wootemw{at}auburn.edu
The neurotrophin nerve growth factor (NGF) supports neuronal survival by activating the transcription factor nuclear factor-
J. Biol. Chem, 10.1074/jbc.M109730200
Submitted on October 9, 2001
Revised on May 6, 2002
Accepted on May 28, 2002
Identification of IRAK as a conserved component in the p75-neurotrophin receptor activation of NF-
B
B (NF-B). We report here for the first time, the identification of p75-associated kinase that mediates NGF driven NF-B activation. Using co-immunoprecipitation, we demonstrate an NGF dependent association of 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-B occurs predominantly through the p75 receptor, TrkA activity suppresses NF-B activation and retards IB
degradation. In addition, we observe a requirement for IRAK’s kinase activity in mediating NGF-induced NF-B activation, recruitment of the adapter protein p62 to the p75 receptor, as well as, cell survival. Moreover, p75-IRAK mediated B activation and the recruitment of IKK, but not IKK
, to the receptor requires 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.
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