p-S177,S181-IKKB:IKKA:pUb-NEMO phosphorylates IkB-alpha:NF-kB

Stable Identifier
R-HSA-202541
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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NF-kB is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins, called IkBs, which mask the nuclear localization signal (NLS) of NF-kB and prevent its nuclear translocation. A key event in NF-kB activation involves phosphorylation of IkB (at sites equivalent to Ser32 and Ser36 of IkB-alpha or Ser19 and Ser22 of IkB-beta) by IKK. The phosphorylated IkB-alpha is recognized by the E3 ligase complex and targeted for ubiquitin-mediated proteasomal degradation, releasing the NF-kB dimer p50/p65 into the nucleus to turn on target genes. (Karin & Ben-Neriah 2000)

Literature References
PubMed ID Title Journal Year
17363905 Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways

Shambharkar, PB, Blonska, M, Pappu, BP, Li, H, You, Y, Sakurai, H, Darnay, BG, Hara, H, Penninger, J, Lin, X

EMBO J 2007
9252186 A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB

DiDonato, JA, Hayakawa, M, Rothwarf, DM, Zandi, E, Karin, M

Nature 1997
15145317 The two NF-kappaB activation pathways and their role in innate and adaptive immunity

Bonizzi, G, Karin, M

Trends Immunol 2004
15371334 Signaling to NF-kappaB

Hayden, MS, Ghosh, S

Genes Dev 2004
8601309 Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity

Chen, ZJ, Parent, L, Maniatis, T

Cell 1996
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of p-S177,S181-IKKB:IKKA:pUb-NEMO [cytosol]
Physical Entity
Activity
Orthologous Events
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Created