PMID- 10195894
OWN - NLM
STAT- MEDLINE
DCOM- 19990504
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 284
IP  - 5412
DP  - 1999 Apr 9
TI  - Positive and negative regulation of IkappaB kinase activity through IKKbeta
      subunit phosphorylation.
PG  - 309-13
AB  - IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK)
      phosphorylates IkappaB inhibitory proteins, causing their degradation and
      activation of transcription factor NF-kappaB, a master activator of inflammatory 
      responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are
      highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian 
      cells, phosphorylation of two sites at the activation loop of IKKbeta was
      essential for activation of IKK by tumor necrosis factor and interleukin-1.
      Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK 
      activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory
      stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine
      cluster. Such phosphorylation decreased IKK activity and may prevent prolonged
      activation of the inflammatory response.
FAU - Delhase, M
AU  - Delhase M
AD  - Laboratory of Gene Regulation and Signal Transduction, Department of
      Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla,
      CA 92093-0636, USA.
FAU - Hayakawa, M
AU  - Hayakawa M
FAU - Chen, Y
AU  - Chen Y
FAU - Karin, M
AU  - Karin M
LA  - eng
GR  - R01 AI43477/AI/NIAID NIH HHS/United States
GR  - R37 ES04151/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 17885-08-4 (Phosphoserine)
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 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - EC 2.7.11.25 (NF-kappa B kinase)
SB  - IM
CIN - Science. 1999 Apr 9;284(5412):271-3. PMID: 10232975
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Cell Line
MH  - DNA-Binding Proteins/metabolism
MH  - Enzyme Activation
MH  - HeLa Cells
MH  - Helix-Loop-Helix Motifs
MH  - Humans
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins
MH  - Interleukin-1/pharmacology
MH  - Leucine Zippers
MH  - *MAP Kinase Kinase Kinase 1
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
AID - 10.1126/science.284.5412.309 [doi]
PST - ppublish
SO  - Science. 1999 Apr 9;284(5412):309-13. doi: 10.1126/science.284.5412.309.