Gene interactions and pathways from curated databases and text-mining

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PTPN11 — STAT3

Pathways - manually collected, often from reviews:

  • OpenBEL Selventa BEL large corpus: STAT3 → PTPN11 (decreases, PTPN11 Activity, STAT3 Activity)
    Evidence: SHP-2 binds to these residues on the leptin receptor via different sites [56]. Binding of SHP-2 to Y985 occurs via a SH2 domain and results in the activation of the enzyme, whereas Y974 likely associates with the active site of the enzyme SHP-2 binds to phosphotyrosine 986, becomes activated and can thus down-regulate further tyrosine phosphorylation-dependent leptin signalling such as STAT3 activation in the hypothalamus.
  • NCI Pathway Database IL6-mediated signaling events: STAT3 (dimer)/FOXO1 complex (STAT3-FOXO1) → GRB2/SOS1/GAB family/SHP2 complex (GRB2-SOS1-GAB1_GAB2-PTPN11) (transcription, activates)
    Kortylewski et al., J Biol Chem 2003, Wegenka et al., Mol Cell Biol 1993, Schaper et al., Biochem J 1998
    Evidence: mutant phenotype, reporter gene, physical interaction, other species

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Banks et al., J Biol Chem 2000 : By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling ; Tyr ( 985 ) controls the tyrosine phosphorylation of SHP-2 , and Tyr ( 1138 ) controls STAT3 activation
Gunaje et al., Biochem Biophys Res Commun 2001 : Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6 induced Stat3 signaling by alpha-thrombin ... Pretreatment of cells with a phosphatase inhibitor reversed the inhibitory actions of alpha-thrombin, suggesting a role for PTP1D in alpha-thrombin mediated inhibition of IL-6 induced Stat3 signaling
Lundin Brockdorff et al., Cytokine 2002 (MAP Kinase Signaling System...) : SHP2 regulates IL-2 induced MAPK activation, but not Stat3 or Stat5 tyrosine phosphorylation, in cutaneous T cell lymphoma cells ... Furthermore, the results indicate that SHP2 may not be involved in the activation of Stat3 or Stat5 in CTCL cells
Pai et al., Biochem Biophys Res Commun 2005 (Stomach Neoplasms) : While JAK inhibition with AG490 significantly reduced leptin induced ERK2, STAT3 phosphorylation, and cell proliferation, SHP2 inhibition only partially reduced cancer cell proliferation
Han et al., Gastroenterology 2005 (Colitis...) : SHP-2 , through binding to the glycoprotein 130 signaling receptor, negatively regulates STAT3 activation
Wang et al., Mol Biol Cell 2006 : Expression of catalytically inactive SHP-2 in DDR1 transfected cells restored the tyrosine phosphorylation of Stat3 and cell migration ... Together, these results demonstrate that SHP-2 is required for the DDR1 induced suppression of Stat1 and Stat3 tyrosine phosphorylation, cell migration, and branching tubulogenesis
Duechting et al., J Virol 2008 (Inflammation) : Analysis of the transcriptional activation of target genes revealed that NS1 induced STAT3 signaling was associated with upregulation of genes involved in immune response ( e.g., the IFNAR1 and IL-2 genes ) and downregulation of genes associated with viral defense ( e.g., the OAS1 and TYK2 genes ) ... The NS1 induced upregulation of STAT3/PIAS3 in the absence of STAT1 phosphorylation and the lack of SOCS1/SOCS3 activation may contribute to the mechanisms by which B19 evades the immune response and establishes persistent infection in human endothelial cells
Park et al., Free Radic Biol Med 2009 : In the presence of H ( 2 ) O ( 2 ), SHP-2 formed a complex with STAT-3 and reduced the steady-state STAT-3 phosphorylation level
Zhang et al., J Biol Chem 2009 (Leukemia, Myelomonocytic, Juvenile...) : Negative regulation of Stat3 by activating PTPN11 mutants contributes to the pathogenesis of Noonan syndrome and juvenile myelomonocytic leukemia
Yuan et al., J Biol Chem 2010 (Breast Neoplasms...) : Furthermore, PTPN9 WT expression specifically impairs EGF induced STAT3 and STAT5 activation, and inhibits the cell growth in soft agar
Jia et al., PloS one 2010 : H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1 : 1-, STAT1 : 3- and STAT3 : 3- DNA complexes