MAPK12 phosphorylates PTPN3

Stable Identifier
Reaction [transition]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
22730326 p38γ Mitogen-activated protein kinase signals through phosphorylating its phosphatase PTPH1 in regulating ras protein oncogenesis and stress response

Suresh, PS, Chen, G, Mirza, SP, Hou, S, Qi, X, Lepp, A

J. Biol. Chem. 2012
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 serine/threonine kinase activity of PTPN3:p-T183,Y185-MAPK12 [cytosol]

Orthologous Events
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