Ankyrin-rich membrane spanning protein plays a critical role in nuclear factor-kappa B signaling.
Activation of nuclear factor-kappaB (NF-kappaB), a key feature of the neurotrophin signaling, has been shown to be critical for neuronal survival under pathologic settings. However, the precise mechanism by which neurotrophins activate NF-kappaB is not well understood. Here we report that the Ankyrin-rich Membrane Spanning (ARMS/Kidins220) protein, a novel transmembrane substrate of tropomyosin receptor kinase B (TrkB), plays an important role in NF-kappaB signaling elicited by brain-derived neurotrophic factor (BDNF). Accordingly, depletion of ARMS by specific RNA interference, or disruption of ARMS-TrkB interaction with expression of dominant-negative ARMS mutant, abolished BDNF-induced signaling to NF-kappaB. Our data further suggests that ARMS may promote NF-kappaB signaling via activation of mitogen-activated kinase (MAPK) and IkappaB kinase (IKK), thereby facilitating phosphorylation of RelA (major NF-kappaB subunit) at an IKK-sensitive site. The results shown here identify ARMS as a major factor that links neurotrophin signaling to NF-kappaB.
Sniderhan
Lynn F
LF
Department of Microbiology and Immunology,University of Rochester Medical Center, Rochester, NY 14642, USA.
Stout
Angela
A
Lu
Yuanan
Y
Chao
Moses V
MV
Maggirwar
Sanjay B
SB
D000818:Animals; D017089:Ankyrin Repeat / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; C482591:KIDINS220 protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins