◀ Back to PIK3R1
PIK3R1 — PTPN11
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
Complex of PIK3R1-PTPN11
→
IL6
(increases)
Hideshima et al., Oncogene 2001*
Evidence: that IL-6 triggers activation of PI3-K and its association with SHP2, inactivates caspase-9, and protects against Dex-induced apoptosis.
-
BioCarta the co-stimulatory signal during t-cell activation:
SHP-2 (PTPN11)
→
PI3K complex (PIK3CA-PIK3R1)
(T cell activation, inhibits)
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KEGG Neurotrophin signaling pathway:
PTPN11
→
PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/PIK3R2/PIK3R3/PIK3R5
(protein-protein, binding/association)
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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
-
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
-
NCI Pathway Database Fc-epsilon receptor I signaling in mast cells:
GAB2/PI3K/SHP2 complex (GAB2-PTPN11-PIK3CA-PIK3R1)
→
AKT1 (AKT1)
(modification, activates)
-
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 IL6-mediated signaling events:
GRB2/SOS1/GAB family/SHP2/PI3K complex (GRB2-SOS1-GAB1_GAB2-PTPN11-PIK3CA-PIK3R1)
→
AKT1 (AKT1)
(modification, activates)
Jee et al., J Invest Dermatol 2002
Evidence: mutant phenotype
-
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 Fc-epsilon receptor I signaling in mast cells:
Antigen/IgE/Fc epsilon R1/Fyn complex (FYN-FCER1A-MS4A2-IGHE-FCER1G)
→
GAB2/PI3K/SHP2 complex (GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, activates)
-
NCI Pathway Database Fc-epsilon receptor I signaling in mast cells:
GAB2 (GAB2)
→
GAB2/PI3K/SHP2 complex (GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, collaborate)
-
NCI Pathway Database Fc-epsilon receptor I signaling in mast cells:
SHP2 (PTPN11)
→
GAB2/PI3K/SHP2 complex (GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, collaborate)
-
NCI Pathway Database Fc-epsilon receptor I signaling in mast cells:
SHP2 (PTPN11)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
-
NCI Pathway Database Fc-epsilon receptor I signaling in mast cells:
GAB2/PI3K/SHP2 complex (GAB2-PTPN11-PIK3CA-PIK3R1)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
-
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 EPO signaling pathway:
SHC (SHC1)
→
GAB1/SHIP/PIK3R1/SHP2/SHC complex (GAB1-INPP5D-PIK3R1-PTPN11-SHC1)
(modification, collaborate)
-
NCI Pathway Database EPO signaling pathway:
Gab1 (GAB1)
→
GAB1/SHIP/PIK3R1/SHP2/SHC complex (GAB1-INPP5D-PIK3R1-PTPN11-SHC1)
(modification, collaborate)
-
NCI Pathway Database EPO signaling pathway:
GAB1/SHIP/PIK3R1/SHP2/SHC complex (GAB1-INPP5D-PIK3R1-PTPN11-SHC1)
→
PIK3R1 (PIK3R1)
(modification, collaborate)
-
NCI Pathway Database EPO signaling pathway:
GAB1/SHIP/PIK3R1/SHP2/SHC complex (GAB1-INPP5D-PIK3R1-PTPN11-SHC1)
→
SHP2 (PTPN11)
(modification, collaborate)
-
NCI Pathway Database EPO signaling pathway:
GAB1/SHIP/PIK3R1/SHP2/SHC complex (GAB1-INPP5D-PIK3R1-PTPN11-SHC1)
→
SHIP (INPP5D)
(modification, collaborate)
-
NCI Pathway Database EPO signaling pathway:
PIK3R1 (PIK3R1)
→
SHP2 (PTPN11)
(modification, collaborate)
-
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 IL6-mediated signaling events:
GRB2/SOS1/GAB family/SHP2 complex (GRB2-SOS1-GAB1_GAB2-PTPN11)
→
PI3K complex (PIK3CA-PIK3R1)
(modification, collaborate)
Takahashi-Tezuka et al., Mol Cell Biol 1998
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
GRB2/SOS1/GAB family/SHP2 complex (GRB2-SOS1-GAB1_GAB2-PTPN11)
→
GRB2/SOS1/GAB family/SHP2/PI3K complex (GRB2-SOS1-GAB1_GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, collaborate)
Takahashi-Tezuka et al., Mol Cell Biol 1998
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database IL6-mediated signaling events:
PI3K complex (PIK3CA-PIK3R1)
→
GRB2/SOS1/GAB family/SHP2/PI3K complex (GRB2-SOS1-GAB1_GAB2-PTPN11-PIK3CA-PIK3R1)
(modification, collaborate)
Takahashi-Tezuka et al., Mol Cell Biol 1998
Evidence: mutant phenotype, physical interaction
-
Reactome Reaction:
PIK3R1
→
PTPN11
(indirect_complex)
Ong et al., Proc Natl Acad Sci U S A 2001, Sun et al., J Biol Chem 2008, Kanai et al., J Biol Chem 1997, Ong et al., Biochem Biophys Res Commun 1997, Hadari et al., Mol Cell Biol 1998
-
Reactome Reaction:
PIK3R1
→
PTPN11
(reaction)
Ong et al., Proc Natl Acad Sci U S A 2001, Sun et al., J Biol Chem 2008, Kanai et al., J Biol Chem 1997, Ong et al., Biochem Biophys Res Commun 1997, Hadari et al., Mol Cell Biol 1998
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
PTPN11
—
PIK3R1
(physical association, affinity chromatography technology)
Takahashi et al., J Cell Physiol 1999*
-
IRef Biogrid Interaction:
PTPN11
—
PIK3R1
(physical association, affinity chromatography technology)
Craddock et al., J Biol Chem 1997
-
IRef Biogrid Interaction:
PTPN11
—
PIK3R1
(physical association, affinity chromatography technology)
Zhang et al., Biochem Biophys Res Commun 1999*
-
MIPS CORUM PDGFRA-PLC-gamma-1-PI3K-SHP-2 complex, PDGF stimulated:
PDGFRA-PLC-gamma-1-PI3K-SHP-2 complex, PDGF stimulated complex (PDGFRA-PIK3R1-PLCG1-PTPN11)
Bazenet et al., Mol Cell Biol 1996*
-
IRef Corum Interaction:
Complex of PDGFRA-PLCG1-PIK3R1-PTPN11
(association, coimmunoprecipitation)
Bazenet et al., Mol Cell Biol 1996*
-
IRef Hprd Interaction:
PTPN11
—
PIK3R1
(in vivo)
Zhang et al., Biochem Biophys Res Commun 1999*
-
IRef Intact Interaction:
Complex of PIK3R1-EGFR-PTPN11-GAB2-GRB2
(association, anti tag coimmunoprecipitation)
Brummer et al., J Biol Chem 2006*
-
IRef Intact Interaction:
Complex of 37 proteins
(association, tandem affinity purification)
Brehme et al., Proc Natl Acad Sci U S A 2009
-
IRef Ophid Interaction:
PIK3R1
—
PTPN11
(aggregation, confirmational text mining)
Zhang et al., Biochem Biophys Res Commun 1999*
-
IRef Ophid Interaction:
PIK3R1
—
PTPN11
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Wu et al., Oncogene 2000
(Brain Neoplasms...) :
Reduced EGF stimulated activation of
PI3-K was
mediated by interactions between carboxyl terminus of SIRPalpha1 and the Src homology-2 (SH2) containing phosphotyrosine phosphatase,
SHP2 ... These data reveal a pathway that negatively regulates EGFR induced
PI3-K activation in glioblastoma cells and
involves interactions between
SHP2 and tyrosine phosphorylated SIRPalpha1
Yart et al., J Biol Chem 2001
:
Indeed, the association of Gab1 with
SHP2 was
blocked by
PI3K inhibitors, and expression of Gab1 mutant deficient for binding to SHP2 was found to inhibit Ras stimulation without interfering with PI3K activation
Wu et al., Oncogene 2001
(Glioblastoma) :
Based on these results, we conclude that SHP-2 is required for mediating PI3K/Akt activation, and the N-terminal SH2 domain is critically important for a `` positive ''
role of
SHP-2 in regulating
PI3K pathway activation
Zhang et al., Mol Cell Biol 2002
:
Our results suggest that, in addition to its role as a positive component of the Ras-Erk pathway,
Shp2 negatively
regulates EGF dependent
PI3K activation by dephosphorylating Gab1 p85 binding sites, thereby terminating a previously proposed Gab1-PI3K positive feedback loop
Hale et al., Proc Natl Acad Sci U S A 2006
:
Additionally, it was found that expression of
NS1 alone was
sufficient to constitutively activate
PI3K , causing the phosphorylation of a downstream mediator of PI3K signal transduction, Akt
Ehrhardt et al., J Virol 2007
:
NS1 binds to and
activates PI3K , which results in the activation of the PI3K effector Akt
Sampaio et al., Mol Cell Biol 2008
:
Indeed, by up- and down-regulation of signal strength in different cell lines and through different methods, we observed that
Gab1/Shp2 and Ras/ERK1-2 in concert become independent of PI3K upon strong epidermal growth factor receptor (EGFR) stimulation and
dependent on
PI3K upon limited EGFR activation
Hale et al., J Biol Chem 2008
:
Overall, these data suggest a model by which
NS1 activates
PI3K catalytic activity by masking a normal regulatory element specific to the p85beta inter-SH2 domain
Gallacher et al., J Physiol 2009
(Influenza, Human) :
This response to virus infection was only partially dependent upon
NS1 mediated activation of
PI3K
Jackson et al., Virology 2010
:
Surprisingly, given previous reports that
NS1 activates
PI3K to prevent apoptosis, the mutant viruses rUd-Y89F and rUd-P164/7A that fail to activate PI3K did not induce any more apoptosis than wild-type virus in MRC-5 and A549 cells, even though these cells are highly sensitive to inducers of apoptosis
Hale et al., Proc Natl Acad Sci U S A 2010
:
Overall, these data suggest that both direct binding of
NS1 to p85beta ( resulting in repositioning of the N-terminal SH2 domain ) and possible NS1 : p110 contacts
contribute to
PI3K activation