3PY3

Crystal structure of phosphorylated p38alpha MAP kinase

Summary for 3PY3

• Entry DOI: 10.2210/pdb3py3/pdb
• Descriptor: Mitogen-activated protein kinase 14 (2 entities in total)
• Functional Keywords: kinase, transferase, phosphorylation
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm: P47811
• Total number of polymer chains: 1
• Total formula weight: 43669.47

Authors

Zhang, Y.Y.,Wu, J.W.,Wang, Z.X. (deposition date: 2010-12-11, release date: 2011-03-16, Last modification date: 2024-11-20)

Primary citation

Zhang, Y.Y.,Wu, J.W.,Wang, Z.X.
Mitogen-activated Protein Kinase (MAPK) Phosphatase 3-mediated Cross-talk between MAPKs ERK2 and p38{alpha}.
J.Biol.Chem., 286:16150-16162, 2011

PubMed Abstract: MAPK phosphatase 3 (MKP3) is highly specific for ERK1/2 inactivation via dephosphorylation of both phosphotyrosine and phosphothreonine critical for enzymatic activation. Here, we show that MKP3 is able to effectively dephosphorylate the phosphotyrosine, but not phosphothreonine, in the activation loop of p38α in vitro and in intact cells. The catalytic constant of the MKP3 reaction for p38α is comparable with that for ERK2. Remarkably, MKP3, ERK2, and phosphorylated p38α can form a stable ternary complex in solution, and the phosphatase activity of MKP3 toward p38α substrate is allosterically regulated by ERK2-MKP3 interaction. This suggests that MKP3 not only controls the activities of ERK2 and p38α but also mediates cross-talk between these two MAPK pathways. The crystal structure of bisphosphorylated p38α has been determined at 2.1 Å resolution. Comparisons between the phosphorylated MAPK structures reveal the molecular basis of MKP3 substrate specificity.

PubMed: 21454500
DOI: 10.1074/jbc.M110.203786

Experimental method

X-RAY DIFFRACTION (2.1 Å)