◀ Back to IL2
IL2 — PIK3CA
Pathways - manually collected, often from reviews:
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NCI Pathway Database IL2 signaling events mediated by PI3K:
None
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, collaborate)
Augustine et al., Mol Cell Biol 1991, Gómez et al., J Immunol 1997
Evidence: assay, other species
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NCI Pathway Database IL2 signaling events mediated by PI3K:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
PKC zeta (PRKCZ)
(modification, activates)
Gómez et al., Exp Cell Res 1995, Gómez et al., J Immunol 1997
Evidence: mutant phenotype, other species
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NCI Pathway Database SHP2 signaling:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database SHP2 signaling:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11)
(modification, collaborate)
Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database SHP2 signaling:
PI3K complex (PIK3CA-PIK3R1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11)
(modification, collaborate)
Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Johnston et al., J Biol Chem 1995
Evidence: physical interaction
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1-PIK3CA-PIK3R1)
(modification, collaborate)
Johnston et al., J Biol Chem 1995
Evidence: physical interaction
-
NCI Pathway Database IL2-mediated signaling events:
PI3K complex (PIK3CA-PIK3R1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/IRS1-2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-IRS2_IRS1-PIK3CA-PIK3R1)
(modification, collaborate)
Johnston et al., J Biol Chem 1995
Evidence: physical interaction
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R beta/gamma/JAK1/Fyn/JAK3 complex (IL2RB-JAK1-FYN-IL2-IL2RG-JAK3)
→
IL2/IL2R beta/gamma/JAK1/Fyn/JAK3/PI3K complex (IL2RB-JAK1-FYN-IL2-IL2RG-JAK3-PIK3CA-PIK3R1)
(modification, collaborate)
Augustine et al., Mol Cell Biol 1991
Evidence: assay, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R beta/gamma/JAK1/Fyn/JAK3 complex (IL2RB-JAK1-FYN-IL2-IL2RG-JAK3)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Augustine et al., Mol Cell Biol 1991
Evidence: assay, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R beta/gamma/JAK1/Fyn/JAK3/PI3K complex (IL2RB-JAK1-FYN-IL2-IL2RG-JAK3-PIK3CA-PIK3R1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Augustine et al., Mol Cell Biol 1991
Evidence: assay, other species
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
None
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, activates)
Gu et al., Mol Cell Biol 2000, Lindemann et al., J Biol Chem 2003, Akbar et al., Eur J Immunol 1996, Ahmed et al., Proc Natl Acad Sci U S A 1997, Reif et al., J Biol Chem 1997
Evidence: mutant phenotype, assay, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K complex (IL2RB-JAK1-LCK-IL2-IL2RG-JAK3-PIK3CA-PIK3R1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Tsujino et al., Genes Cells 1999, Merida et al., J Immunol 1991, Taichman et al., J Biol Chem 1993, González-García et al., J Biol Chem 1997
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K complex (IL2RB-JAK1-LCK-IL2-IL2RG-JAK3-PIK3CA-PIK3R1)
→
IL2/IL2R beta/gamma/JAK1/LCK/JAK3 complex (IL2RB-JAK1-LCK-IL2-IL2RG-JAK3)
(modification, collaborate)
Tsujino et al., Genes Cells 1999, Merida et al., J Immunol 1991, Taichman et al., J Biol Chem 1993, González-García et al., J Biol Chem 1997
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
PI3K complex (PIK3CA-PIK3R1)
→
IL2/IL2R beta/gamma/JAK1/LCK/JAK3 complex (IL2RB-JAK1-LCK-IL2-IL2RG-JAK3)
(modification, collaborate)
Tsujino et al., Genes Cells 1999, Merida et al., J Immunol 1991, Taichman et al., J Biol Chem 1993, González-García et al., J Biol Chem 1997
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997, Gadina et al., J Immunol 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11)
(modification, collaborate)
Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997, Gadina et al., J Immunol 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
PI3K complex (PIK3CA-PIK3R1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11)
(modification, collaborate)
Gadina et al., J Biol Chem 2000, Gu et al., Mol Cell Biol 2000, Merida et al., J Immunol 1991, Truitt et al., J Biol Chem 1994, Kanazawa et al., Cell Immunol 1994, Gómez et al., J Immunol 1997, Gadina et al., J Immunol 1999
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL2 signaling events mediated by STAT5:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
→
STAT5 (dimer)-active (STAT5B/STAT5A)
(transcription, activates)
Moriggl et al., Immunity 1999, Brennan et al., Immunity 1997
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL2-mediated signaling events:
RAF1 (RAF1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, activates)
Blanchard et al., Oncogene 2000, Lundin Brockdorff et al., Cytokine 2002, Karnitz et al., Mol Cell Biol 1995
Evidence: mutant phenotype, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SYK complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SYK)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, activates)
Jiang et al., Blood 2003
Evidence: mutant phenotype
-
NCI Pathway Database SHP2 signaling:
RAF1 (RAF1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GRB2/SOS1/GAB2/SHP2/PI3K complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1-GRB2-SOS1-GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, activates)
Blanchard et al., Oncogene 2000, Lundin Brockdorff et al., Cytokine 2002, Karnitz et al., Mol Cell Biol 1995
Evidence: mutant phenotype
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K complex (IL2RB-JAK1-LCK-IL2-IL2RG-JAK3-PIK3CA-PIK3R1)
→
BCL-X (BCL2L1)
(transcription, activates)
González-García et al., J Biol Chem 1997
Evidence: mutant phenotype, other species
-
Reactome Reaction:
IL2
→
PIK3CA
(indirect_complex)
-
Reactome Reaction:
IL2
→
PIK3CA
(reaction)
Wickrema et al., J Biol Chem 1999, Gu et al., Mol Cell 1998
Text-mined interactions from Literome
Ciprés et al., Eur J Immunol 1999
:
The requirement for
IL-2 induced
PI3K activity in suppressing the onset of apoptotic cell death is discussed
Harada et al., J Biol Chem 2001
:
In contrast, the N191A mutant, which retains PI3K binding ability, resulted in a complete abrogation of activity, suggesting that
PI3K mediates a negative effect upon transcriptional activation of the
IL-2 gene ... Taken together, these data indicate that
PI3K , when associated with the YMNM motif, may
act as a negative mediator in CD28 mediated
IL-2 gene transcription
Phu et al., J Leukoc Biol 2001
:
IL-2 synthesis by anti-CD3 activated CD8 ( + ) T cells was also
diminished by
PI3-K inhibition ... These results support the conclusion that
PI3-K activation is
involved in T-cell receptor, CD28, and
IL-2 receptor signaling of CD8 ( + ) T cells
Heijink et al., Eur J Immunol 2003
:
Together, our results indicate that increased
IL-2 dependent
PI3-K signaling leads to impaired negative feedback control of the production of Th2-type cytokine IL-5 by the cAMP dependent pathway
Chakraborty et al., Neuroscience 2003
:
Activation of
PI3K by
IL-2 was also blocked by tyrphostin A25, a selective inhibitor of PTK, suggesting activation of the latter by IL-2 is upstream to PI3K activation
Williams et al., J Immunol 2004
(Disease Susceptibility...) :
Inhibition of
PI3K resulted in increased serum levels of IL1-beta,
IL-2 , IL-6, IL-10, IL-12, and TNF-alpha in septic mice
Brando-Lima et al., Int Immunopharmacol 2006
:
This effect is inhibited by D-galactose and PI3K inhibitors, and is accompanied by an increase in IL-2 receptor expression and by a
PI3K dependent
IL-2 gene expression and IL-2 protein synthesis
Sanchez-Lockhart et al., J Immunol 2006
:
CD28 signaling through
PI3K results in the recruitment of protein kinase C (PKC)theta to the cSMAC, activation of NF-kappaB, and
induction of
IL-2 transcription
Marzec et al., Blood 2008
(Lymphoma, T-Cell, Cutaneous) :
The mTORC1,
PI3K/Akt , and MEK/ERK pathways could also be
activated by
IL-2 in the primary leukemic, mitogen preactivated CTCL cells
Venkatachalam et al., Am J Physiol Heart Circ Physiol 2008
(Hyperglycemia) :
Resveratrol inhibits high glucose induced
PI3K/Akt/ERK dependent
interleukin-17 expression in primary mouse cardiac fibroblasts
Zheng et al., J Immunol 2008
(HIV Infections) :
We demonstrate that
IL-2 initially
requires both STAT5 and
PI3K activation to increase expression of IL-2Rbeta, produce granulysin, and kill C. neoformans
Gentle et al., J Immunol 2012
:
Modulation required de novo protein synthesis, and
PI3K , JNK, and ERK activity were
necessary for enhanced
IL-2 expression, whereas modulation of IL-10 required only PI3K activity
Monfar et al., Mol Cell Biol 1995
:
We demonstrate that these kinases lie on the same signalling pathway and that
PI3K mediates the activation of pp70 by the cytokine
interleukin-2 (IL-2) ... Like rapamycin, PKA appears to act downstream of cPKC mediated pp70S6k activation, and like wortmannin, PKA antagonizes
IL-2 dependent activation of
PI3K
Ghiotto-Ragueneau et al., Eur J Immunol 1996
:
Worthmannin, a specific inhibitor of
PI3-K enzymatic activity within the nanomolar range also
inhibits the
interleukin-2 production induced by costimulation mediated by either the B7.1- and B7.2 transfected cells or CD28 monoclonal antibodies
Bavelloni et al., J Cell Sci 1999
(Osteosarcoma) :
Phosphatidylinositol 3-kinase translocation to the nucleus is
induced by
interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells