Meta-Biol

• Pathways

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).