PTPN3 dephosphorylates MAPK12

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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).

Literature References
PubMed ID Title Journal Year
15851477 Essential role of p38gamma in K-Ras transformation independent of phosphorylation

Chen, G, Qi, X, Mercola, D, Tang, J, Han, J

J. Biol. Chem. 2005
25314968 Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain-modulated complex formation

Wang, AH, Chen, KE, Santhanam, A, Meng, TC, Ho, MR, Chou, CC, Lin, SY, Wu, MJ

Sci Signal 2014
20332238 PTPH1 dephosphorylates and cooperates with p38gamma MAPK to increase ras oncogenesis through PDZ-mediated interaction

Chen, G, Pohl, N, Zhi, HY, Basir, Z, Qi, XM, Li, RS, Loesch, M, Hou, SW

Cancer Res. 2010
Catalyst Activity

protein tyrosine phosphatase activity of PTPN3:p-T183,Y185-MAPK12 [cytosol]

Orthologous Events
Cite Us!