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p-Y693-STAT4 dimerizes
Stable Identifier
R-HSA-8950778
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
Synonyms
p-STAT4 homodimerization
ReviewStatus
5/5
Locations in the PathwayBrowser
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Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-12 family signaling (Homo sapiens)
Interleukin-12 signaling (Homo sapiens)
p-Y693-STAT4 dimerizes (Homo sapiens)
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Cell stimulation by Interleukin-12 (IL12) leads to formation of Signal transducer and activator of transcription 4 (STAT4) dimers but not heterodimers with STAT1 or STAT3 (Naeger et al. 1999).
STAT4 is required to mediate IL12 effects and is crucial for T cell helper 1 (Th1) development and efficient Interferon gamma (IFNG) production, as shown by STAT4 knock-out studies (Kaplan et al. 1996, Thierfelder et al. 1996). STAT4 is activated by the interaction of IL12 with the interleukin-12 receptor. The interaction of the STAT4 SH2 domain is specific for the peptide sequence pYLPSNID, which contains tyrosine 800 in the Interleukin-12 receptor beta 2 subunit (IL12RB2). This tyrosine is required for STAT4 DNA binding activity and transcriptional activation of the Interferon regulatory factor 1(IRF1) gene.
STAT4 is not capable of binding other peptide sequences at tyrosine residues 678 or 767 of IL12RB2 and these peptides are not required for STAT4 activation.
The Interleukin-12 receptor peptide sequence pYLPSNID appears to be a specific binding site for STAT4, other STATs, including STAT1, which has a closely related SH2 domain, do not recognize pYLPSNID peptides (Naeger et al. 1999).
Literature References
PubMed ID
Title
Journal
Year
9890938
Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling
Hoey, T
,
McKinney, J
,
Salvekar, A
,
Naeger, LK
J. Biol. Chem.
1999
Participants
Input
x 2
p-Y693-STAT4 [cytosol]
(Homo sapiens)
Output
p-Y693-STAT4 dimer [cytosol]
(Homo sapiens)
Participates
as an event of
Interleukin-12 signaling (Homo sapiens)
Orthologous Events
p-Y693-STAT4 dimerizes (Bos taurus)
p-Y693-STAT4 dimerizes (Caenorhabditis elegans)
p-Y693-STAT4 dimerizes (Canis familiaris)
p-Y693-STAT4 dimerizes (Dictyostelium discoideum)
p-Y693-STAT4 dimerizes (Drosophila melanogaster)
p-Y693-STAT4 dimerizes (Gallus gallus)
p-Y693-STAT4 dimerizes (Mus musculus)
p-Y693-STAT4 dimerizes (Sus scrofa)
p-Y693-STAT4 dimerizes (Xenopus tropicalis)
Authored
Duenas, C (2016-12-02)
Reviewed
van de Vosse, E (2017-05-12)
Created
Duenas, C (2016-12-02)
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