Search results for PTPN3

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Protein (3 results from a total of 3)

Identifier: R-HSA-8867650
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PTPN3: P26045
Identifier: R-HSA-5490317
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: PTPN3: P26045
Identifier: R-HSA-8868111
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: P26045

Reaction (5 results from a total of 5)

Identifier: R-HSA-8867047
Species: Homo sapiens
Compartment: plasma membrane
While the roles of EGFR and EPS15 phosphorylation and ubiquitination are not completely clear, recent evidence supports the idea that EGFR-mediated phosphorylation of EPS15 promotes the clustering of the activated receptor into clathrin-coated pits, while the dephosphorylated EPS15 targets EGFR for endocytosis through a caveolin-and lipid raft-dependent route (reviewed in van Bergen en Henegouwen, 2009). Consistent with this, overexpression of the phosphatase PTPN3, which dephosphorylates EPS15 in vitro and in vivo, promotes the internalization of EGFR into caveolin-enriched structures and targets it for lysosomal degradation (Li et al, 2015).
Identifier: R-HSA-8867658
Species: Homo sapiens
Compartment: cytosol
PTPN3-mediated dephosphorylation of MAPK12 promotes RAS signaling and transformation through an unknown mechanism (Tang et al, 2005; Hou et al, 2010; Chen et al, 2014). Consistent with a role for dephosphorylated MAPK12 and PTPN3 in promoting RAS signaling, depletion of PTPN3 or MAPK12 inhibits malignant growth in RAS-activated human cancer cell lines and in mouse models. In addition, RAS signaling increases protein levels of both MAPK12 and PTPN3, suggesting the presence of a positive feedback loop (Hou et al, 2010). Dephosphorylation of MAPK12 may promote its incorporation into complexes with ERK proteins, though the functional significance of this is unclear (Tang et al, 2005).
Identifier: R-HSA-8868118
Species: Homo sapiens
Compartment: cytosol
PTPN3 has been shown to bind to phosphorylated MAPK12 and promote its dephosphorylation, and this interaction is correlated with increased oncogenic signaling through RAS (Hou et al, 2010; Tang et al, 2005; Chen et al, 2014 ). Although the mechanism for this PTPN3 and MAPK12-dependent activation of RAS signaling is not known, dephosphorylation of MAPK12 allows the recovery of larger amounts of MAPK12 from a complex with ERK proteins, suggesting a possible mechanism. A more recent study, however, has found that PTPN3 is itself phosphorylated in a MAPK12-dependent fashion upon binding with phospho-MAPK12. This phosphorylation antagonizes SOB-induced growth inhibition and increases RAS-dependent oncogenic growth (Hou et al, 2012).
Identifier: R-HSA-8867654
Species: Homo sapiens
Compartment: cytosol
PTPN3 is a protein phosphatase that dephosphorylates MAPK12, also known as p38 gamma. Phosphorylation of the p38 family of MAPK is associated with suppression of RAS signaling, and consistent with this, binding and dephosphorylation of MAPK12 by PTPN3 promotes RAS-induced transformation (Tang et al, 2005; Hou et al, 2010; Chen et al, 2014).
Dephosphorylation is promoted by a direct binding between phosphorylated MAPK12 and PTPN3, mediated by an interaction between the PTPN3 PDZ domain and the isoform-specific ETPL domain of MAPK12. Binding of PTPN3 and phosphorylated MAPK12 relieves an autoinhibitory conformation of the phosphatase and promotes MAPK12 dephosphorylation (Hou et al, 2010; Chen et al, 2014). How dephosphorylated MAPK12 promotes RAS signaling remains to be elucidated.
Identifier: R-HSA-8867041
Species: Homo sapiens
Compartment: plasma membrane
EPS15 is phosphorylated at Y849 by activated EGFR (Confalonieri et al, 2000). While the roles of phosphorylation and ubiquitination in EGFR endocytosis are unclear, emerging evidence suggests that EPS15 phosphorylation may target the activated EGFR complex for endocytosis through a clathrin-mediated route, while dephosphorylation at Y849 may direct the receptor complex into a clathrin-independent route (Confalonieri et al, 2002; de Melker et al, 2004; Li et al, 2015; reviewed in van Bergen en Henegouwen, 2009).

Complex (2 results from a total of 2)

Identifier: R-HSA-8867651
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8868113
Species: Homo sapiens
Compartment: cytosol
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