IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3

Stable Identifier
R-HSA-6784323
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol, extracellular region, plasma membrane
ReviewStatus
5/5
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IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3
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STAT3 is recruited directly to the receptor complex via either of the two tyrosine residues in the IL10R1 cytoplasmic domain (Y446 and Y496) that become phosphorylated in response to IL-10 (Weber-Nordt et al. 1996, Riley et al. 1999). Overexpression of a dominant negative mouse Stat3 mutant or an inducibly-active form of mouse Stat3 demonstrated that Stat3 activation is necessary and sufficient to mediate inhibition of macrophage proliferation by IL-10 (O'Farrell et al. 1998) at least in part via enhancement of CDKN2D (INK4d) and CDKN1A (CIP1) expression (O'Farrell et al. 2000). In contrast, the Stat3 mutant did not detectably impair IL-10's ability to inhibit LPS-induced monokine production suggesting that IL10 inhibition of macrophage proliferation and monokine production are the result of two distinct signaling pathways (O'Farrell et al. 1998). Stat3 conditional knockout mice develop chronic enterocholitis and have macrophages that show no response to IL10 (Riley et al. 1999, Takeda et al. 1999).
Literature References
PubMed ID Title Journal Year
8662928 Receptors for interleukin (IL)-10 and IL-6-type cytokines use similar signaling mechanisms for inducing transcription through IL-6 response elements

Lai, CF, Ripperger, J, Morella, KK, Jurlander, J, Hawley, TS, Carson, WE, Kordula, T, Caligiuri, MA, Hawley, RG, Fey, GH, Baumann, H

J. Biol. Chem. 1996
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Orthologous Events
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Bos taurus)
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Canis familiaris)
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Gallus gallus)
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Mus musculus)
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Rattus norvegicus)
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Sus scrofa)
IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3 (Xenopus tropicalis)
Authored
Jupe, S  (2015-06-17)
Reviewed
Meldal, BH  (2016-09-05)
Created
Jupe, S  (2015-06-19)
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