PMID- 10490984
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 7
DP  - 1999 Oct 1
TI  - The signal transduction pathway of CD23 (Fc epsilon RIIb) targets I kappa B
      kinase.
PG  - 3851-7
AB  - Alveolar macrophages play a crucial role in initiating the inflammatory response 
      in allergic asthma through the cross-linking of the low affinity IgE receptors
      (Fc epsilon RIIb or CD23) by IgE-allergen immunocomplexes. We have previously
      shown that CD23 cross-linking in monocytes and U937 cells targets I kappa B
      alpha, leading to the activation of the transcription factor NF-kappa B. We
      demonstrate in this paper that CD23-initiated signaling in U937 cells leads to
      hyperphosphorylation of I kappa B alpha at Ser32/Ser36 residues. Overexpression
      of a dominant-negative I kappa B alpha transgene containing mutations at
      Ser32/Ser36 completely inhibits degradation of I kappa B alpha, NF-kappa B
      activation, and gene transcription that follows CD23 cross-linking. Investigation
      of the second messengers mediating the CD23-dependent activation of NF kappa B
      demonstrates that I kappa B kinases (IKKs) but not p90rsk are selectively
      activated following CD23 cross-linking and mediates the phosphorylation of I
      kappa B alpha. Cotransfection experiments with an IKK beta negative dominant
      completely inhibit CD23 induced NF kappa B activation. Furthermore, the
      activation of tyrosine kinase(s) by CD23 is required for the induction of IKK
      activity, I kappa B alpha degradation, and NF-kappa B nuclear translocation.
      Taken together, our results show that CD23 cross-linking in the monocytic lineage
      induces tyrosine kinase activation followed by activation of IKK, which
      phosphorylates I kappa B alpha at the N-terminal domain (Ser32/Ser36), inducing
      its degradation, NF-kappa B activation and gene transcription.
FAU - Ten, R M
AU  - Ten RM
AD  - Division of Allergy and Department of Immunology, Mayo Clinic, Rochester, MN
      55902, USA. ten.rosa@mayo.edu
FAU - McKinstry, M J
AU  - McKinstry MJ
FAU - Trushin, S A
AU  - Trushin SA
FAU - Asin, S
AU  - Asin S
FAU - Paya, C V
AU  - Paya CV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I kappa B beta protein)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Immune Sera)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Receptors, IgE)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 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)
SB  - AIM
SB  - IM
MH  - DNA-Binding Proteins/metabolism/physiology
MH  - Humans
MH  - I-kappa B Kinase
MH  - *I-kappa B Proteins
MH  - Immune Sera/metabolism
MH  - Mutagenesis, Site-Directed
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/genetics/immunology/*metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Receptors, IgE/immunology/metabolism/*physiology
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Serine/genetics/metabolism
MH  - Signal Transduction/*immunology
MH  - U937 Cells
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - ji_v163n7p3851 [pii]
PST - ppublish
SO  - J Immunol. 1999 Oct 1;163(7):3851-7.