PMID- 10415122
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20141120
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 368
IP  - 1
DP  - 1999 Aug 1
TI  - Direct interaction of STAT4 with the IL-12 receptor.
PG  - 147-55
AB  - Signal transduction by interleukin-12 (IL-12) requires phosphorylation and
      activation of STAT4. Direct interaction of the SH2 domain of STAT4 with a
      phosphotyrosine residue in the IL-12 receptor has been proposed to be required
      for the subsequent STAT4 phosphorylation. The IL-12 receptor beta2 subunit
      contains three tyrosine residues in its cytoplasmic domain. To test the
      hypothesis that one of these tyrosines is involved in binding STAT4,
      phosphopeptides were synthesized according to the amino acid sequences
      surrounding each of these tyrosine residues. Only the phosphopeptide containing
      pTyr800 strongly bound to STAT4 in a cell-free binding assay. When this
      phosphopeptide was introduced into TALL-104 cells, it blocked IL-12-induced STAT4
      phosphorylation by competing with the IL-12 receptor for binding to STAT4. A
      series of alanine replacements was performed in this phosphopeptide to elucidate 
      which amino acids surrounding the pTyr800 residue are critical for STAT4 binding.
      To summarize, the site on the IL-12 receptor which binds STAT4 can be described
      as -T-X-X-G-pY(800)-L-, where the core G-pY(800)-L motif is critical for the
      binding; the threonine at the pY-4 position has only a minor contribution and X
      represents amino acids not critical for the binding. These results demonstrate
      that only a small region of the IL-12 receptor is critically involved in binding 
      STAT4 and suggest the feasibility that small molecule inhibitors could be
      identified which interfere with IL-12 signal transduction for treatment of
      autoimmune diseases.
CI  - Copyright 1999 Academic Press.
FAU - Yao, B B
AU  - Yao BB
AD  - Pharmaceutical Products Division, Pharmaceutical Discovery, Abbott Park,
      Illinois, 60064, USA. betty.yao@abbott.com
FAU - Niu, P
AU  - Niu P
FAU - Surowy, C S
AU  - Surowy CS
FAU - Faltynek, C R
AU  - Faltynek CR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IL12RB2 protein, human)
RN  - 0 (Phosphopeptides)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-12)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT4 Transcription Factor)
RN  - 0 (STAT4 protein, human)
RN  - 0 (Trans-Activators)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - DNA-Binding Proteins/chemistry/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Phosphopeptides/chemistry/metabolism
MH  - Phosphorylation
MH  - Receptors, Interleukin/chemistry/*metabolism
MH  - Receptors, Interleukin-12
MH  - Recombinant Proteins/chemistry/metabolism
MH  - STAT4 Transcription Factor
MH  - Signal Transduction
MH  - Trans-Activators/chemistry/*metabolism
MH  - Tyrosine/chemistry
MH  - src Homology Domains
EDAT- 1999/07/23 00:00
MHDA- 1999/07/23 00:01
CRDT- 1999/07/23 00:00
PHST- 1999/07/23 00:00 [pubmed]
PHST- 1999/07/23 00:01 [medline]
PHST- 1999/07/23 00:00 [entrez]
AID - 10.1006/abbi.1999.1302 [doi]
AID - S0003-9861(99)91302-4 [pii]
PST - ppublish
SO  - Arch Biochem Biophys. 1999 Aug 1;368(1):147-55. doi: 10.1006/abbi.1999.1302.