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

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

Stable Identifier

R-HSA-202541

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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

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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
9252186	A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB Rothwarf, DM, Karin, M, Zandi, E, DiDonato, JA, Hayakawa, M	Nature	1997
17363905	Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways Sakurai, H, Pappu, BP, Hara, H, Li, H, Lin, X, Darnay, BG, Shambharkar, PB, You, Y, Blonska, M, Penninger, J	EMBO J	2007
15145317	The two NF-kappaB activation pathways and their role in innate and adaptive immunity Karin, M, Bonizzi, G	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 Parent, L, Chen, ZJ, Maniatis, T	Cell	1996