◀ Back to IL4
IL4 — IRS2
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
Complex of GRB2-IRS2
→
IL4
(increases)
Zamorano et al., Cell Res 2001*
Evidence: association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL4 treatment although both proteins were expressed IL4 induced association of IRS2 with GRB2 in B cell blasts
-
OpenBEL Selventa BEL large corpus:
IRS2
→
IL4
(increases)
Kruse et al., Respir Res 2002*
Evidence: The sentence from Jubilant IL4 induced phosphorylation of IRS2. Phosphorylation was more in variant R551 than in wildtype Q551 cells.
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NCI Pathway Database IL4-mediated signaling events:
BCL6 (BCL6)
→
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES-IRS2)
(T-helper 2 cell differentiation, inhibits)
Wurster et al., Mol Cell Biol 2002, Swain et al., J Immunol 1990, Shimoda et al., Nature 1996, Kaplan et al., Immunity 1996, Dent et al., Science 1997, Dent et al., Proc Natl Acad Sci U S A 1998
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL4-mediated signaling events:
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES-IRS2)
→
STAT6 (dimer) complex (STAT6)
(T-helper 2 cell differentiation, activates)
Wurster et al., Mol Cell Biol 2002, Swain et al., J Immunol 1990, Shimoda et al., Nature 1996, Kaplan et al., Immunity 1996, Dent et al., Science 1997, Dent et al., Proc Natl Acad Sci U S A 1998
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL4-mediated signaling events:
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES-IRS2)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Jiang et al., J Immunol 2001, Wurster et al., Mol Cell Biol 2002, Sun et al., Nature 1995, Izuhara et al., Blood 1996
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL4-mediated signaling events:
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES)
→
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES-IRS2)
(modification, collaborate)
Jiang et al., J Immunol 2001, Johnston et al., J Biol Chem 1995, Sun et al., Nature 1995
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL4-mediated signaling events:
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES)
→
IRS2 (IRS2)
(modification, collaborate)
Jiang et al., J Immunol 2001, Johnston et al., J Biol Chem 1995, Sun et al., Nature 1995
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL4-mediated signaling events:
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2 complex (IL4-IL4R-JAK1-IL2RG-JAK3-FES-IRS2)
→
IRS2 (IRS2)
(modification, collaborate)
Jiang et al., J Immunol 2001, Johnston et al., J Biol Chem 1995, Sun et al., Nature 1995
Evidence: mutant phenotype, physical interaction, other species
Text-mined interactions from Literome
Gingras et al., Mol Endocrinol 2000
(Breast Neoplasms) :
IL-4 rapidly
induced IRS-1 and
IRS-2 phosphorylation in ZR-75-1 human breast cancer cell lines
Giallourakis et al., J Biol Chem 2000
:
However, no differential activation of STAT6, Akt,
IRS-2 , or p70 ( S6k ), in
response to
IL-4 , was observed in these cells
Zhu et al., J Exp Med 2000
:
It was found that
IL-4 induced phosphorylation of Janus kinases 1 and 3, IL-4R alpha, signal transducer and activator of transcription 6, and
insulin receptor substrate 2 was strikingly but transiently inhibited by TCR ligation both in conventional and TCR transgenic T cells
Jiang et al., J Immunol 2001
:
Fes mediates the
IL-4 activation of
insulin receptor substrate-2 and cellular proliferation ... Overexpression of kinase-inactive Fes blocks the
IL-4 activation of
insulin receptor substrate-2 , but not STAT6
Zamorano et al., Cell Res 2001
:
IL-4 induced the tyrosine phosphorylation of
IRS2 in resting B lymphocytes and in LPS- or CD40L activated blasts ... However,
IL-4 induced association of
IRS2 with GRB2 in B cell blasts
Gingras et al., J Steroid Biochem Mol Biol 2001
:
We have also found that
IL-4 rapidly
induced IRS-1 and
IRS-2 phosphorylation in these cell lines
Kelly-Welch et al., J Immunol 2004
:
IL-4 induced tyrosine phosphorylation of
IRS2 was elevated in Tg ( + ) B cells, whereas IL-4 induced phosphorylation of STAT6 was similar between Tg ( + ) and Tg ( - ) B cells
Prokopchuk et al., Br J Cancer 2005
(Pancreatic Neoplasms) :
Interleukin-4 enhanced activity of MAPK, Akt-1, and Stat3 in IL-4-responsive, but not in IL-4-unresponsive MIA PaCa-2 cells ; however,
IL-4 enhanced tyrosine phosphorylation of
insulin receptor substrate-1 and -2 in all cell lines
O'Connor et al., J Immunol 2007
(Diabetes Mellitus, Type 2) :
Examination of IL-4 signaling in db/db macrophages revealed that
IL-4 dependent
IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages ... These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired
IL-4 dependent
IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4 dependent production of IL-1RA
Heller et al., Science signaling 2008
:
Type I
IL-4Rs selectively
activate IRS-2 to induce target gene expression in macrophages ...
IL-4 induced highly efficient, gammaC dependent tyrosine phosphorylation of
insulin receptor substrate 2 (IRS-2) , whereas IL-13 was less effective, even when phosphorylation of signal transducer and activator of transcription 6 ( STAT6 ) was maximal
Johnston et al., J Biol Chem 1995
:
We report here that IL-2, IL-7, and IL-15, as well as
IL-4 , rapidly
stimulate the tyrosine phosphorylation of IRS-1 and
IRS-2 in human peripheral blood T cells, NK cells, and in lymphoid cell lines
Izuhara et al., Biochem Biophys Res Commun 1996
:
In both cell lines,
IL-4 induced tyrosine phosphorylation of
IRS-2 , association of PI3 kinase with IRS-2, and FES or a FES related protein
Takeda et al., J Mol Med (Berl) 1997
:
Two cytoplasmic proteins, signal transducer and activator of transcription ( STAT ) 6 and
IL4 induced phosphotyrosine
substrate/insulin receptor substrate 2 ( 4PS/IRS2 ), are activated in IL4 signal transduction