PMID- 10521409
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 43
DP  - 1999 Oct 22
TI  - IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the
      transactivation domain.
PG  - 30353-6
AB  - Recent investigations have elucidated the cytokine-induced NF-kappaB activation
      pathway. IkappaB kinase (IKK) phosphorylates inhibitors of NF-kappaB (IkappaBs). 
      The phosphorylation targets them for rapid degradation through a
      ubiquitin-proteasome pathway, allowing the nuclear translocation of NF-kappaB. We
      have examined the possibility that IKK can phosphorylate the p65 NF-kappaB
      subunit as well as IkappaB in the cytokine-induced NF-kappaB activation. In the
      cytoplasm of HeLa cells, the p65 subunit was rapidly phosphorylated in response
      to TNF-alpha in a time dependent manner similar to IkappaB phosphorylation. In
      vitro phosphorylation with GST-fused p65 showed that a p65 phosphorylating
      activity was present in the cytoplasmic fraction and the target residue was
      Ser-536 in the carboxyl-terminal transactivation domain. The endogenous IKK
      complex, overexpressed IKKs, and recombinant IKKbeta efficiently phosphorylated
      the same Ser residue of p65 in vitro. The major phosphorylation site in vivo was 
      also Ser-536. Furthermore, activation of IKKs by NF-kappaB-inducing kinase
      induced phosphorylation of p65 in vivo. Our finding, together with previous
      observations, suggests dual roles for IKK complex in the regulation of
      NF-kappaB.IkappaB complex.
FAU - Sakurai, H
AU  - Sakurai H
AD  - Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 16-89 Kashima 3-chome,
      Yodogawa-ku, Osaka 532-8505, Japan. hsakurai@tanabe.co.jp
FAU - Chiba, H
AU  - Chiba H
FAU - Miyoshi, H
AU  - Miyoshi H
FAU - Sugita, T
AU  - Sugita T
FAU - Toriumi, W
AU  - Toriumi W
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Macromolecular Substances)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (Chuk protein, mouse)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
RN  - EC 2.7.11.10 (Ikbke protein, mouse)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Nucleus/*metabolism
MH  - Chickens
MH  - Cytoplasm/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - I-kappa B Kinase
MH  - Macromolecular Substances
MH  - Mice
MH  - Molecular Sequence Data
MH  - NF-kappa B/*chemistry/*metabolism
MH  - Phosphates/pharmacology
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - *Serine
MH  - Substrate Specificity
MH  - *Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Xenopus
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1074/jbc.274.43.30353 [doi]
AID - S0021-9258(19)51689-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 22;274(43):30353-6. doi: 10.1074/jbc.274.43.30353.