PMID- 10433356
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20051116
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 19
IP  - 6
DP  - 1999 Jun
TI  - The interleukin-10 signal transduction pathway and regulation of gene expression 
      in mononuclear phagocytes.
PG  - 563-73
AB  - Interleukin-10 (IL-10) activates a diverse array of functional responses in
      mononuclear phagocytes. Functional IL-10 receptor (IL-10R) complexes are
      tetramers consisting of two IL-10R1 polypeptide chains and two IL-10R2 chains.
      Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation
      of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2. These kinases
      then phosphorylate specific tyrosine residues (Y446 and Y496) on the
      intracellular domain of the IL-10R1 chain. Once phosphorylated, these tyrosine
      residues (and their flanking peptide sequences) serve as temporary docking sites 
      for the latent transcription factor, STAT3 (signal transducer and activator of
      transcription-3). STAT3 binds to these sites via its SH2 (Src homology 2) domain,
      and is, in turn, tyrosine-phosphorylated by the receptor-associated JAKs. It then
      homodimerizes and translocates to the nucleus where it binds with high affinity
      to STAT-binding elements (SBE) in the promoters of various IL-10-responsive
      genes. One of these genes, SOCS-3 (Suppressor of Cytokine Signaling-3) is a
      member of a newly identified family of genes that inhibit JAK/STAT-dependent
      signaling. Moreover, the ability of IL-10 to induce de novo synthesis of SOCS-3
      in monocytes correlates with its ability to inhibit expression of many genes in
      these cells, including endotoxin-inducible cytokines such as tumor necrosis
      factor-alpha (TNF-alpha) and IL-1. Thus, the ability of IL-10 to inhibit gene
      expression in monocytes is associated with its ability to rapidly induce
      synthesis of SOCS-3.
FAU - Donnelly, R P
AU  - Donnelly RP
AD  - Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food 
      and Drug Administration, Bethesda, MD 20892, USA. donnelly@cber.fda.gov
FAU - Dickensheets, H
AU  - Dickensheets H
FAU - Finbloom, D S
AU  - Finbloom DS
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Lipopolysaccharides)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Humans
MH  - Interferons/pharmacology
MH  - Interleukin-10/*physiology
MH  - Interleukin-4/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Monocytes/*physiology
MH  - Signal Transduction/*physiology
RF  - 82
EDAT- 1999/08/05 00:00
MHDA- 1999/08/05 00:01
CRDT- 1999/08/05 00:00
PHST- 1999/08/05 00:00 [pubmed]
PHST- 1999/08/05 00:01 [medline]
PHST- 1999/08/05 00:00 [entrez]
AID - 10.1089/107999099313695 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 1999 Jun;19(6):563-73. doi: 10.1089/107999099313695.