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Publication Abstract from PubMed

The human protein tyrosine phosphatase non-receptor type 4 (PTPN4) prevents cell death induction in neuroblastoma and glioblastoma cell lines in a PDZ-PDZ binding motifs (PBMs) dependent manner but the cellular partners of PTPN4 involved in cell protection are unknown. Here, we described the Mitogen-Activated protein kinase p38gamma as a cellular partner of PTPN4. The main contribution to the p38gamma:PTPN4 complex formation is the tight interaction between the C-terminus of p38gamma and the PDZ domain of PTPN4. We solved the crystal structure of the PDZ domain of PTPN4 bound to the p38gamma C-terminus. We identified the molecular basis of recognition of the C-terminal sequence of p38gamma that displays the highest affinity amongst all endogenous partners of PTPN4. We showed that the p38gamma C-terminus is also an efficient inducer of cell death after its intracellular delivery. In addition to recruiting the kinase, the binding of the C-terminal sequence of p38gamma to PTPN4 abolishes the catalytic auto-inhibition of PTPN4 and thus activates the phosphatase that can efficiently dephosphorylate the activation loop of p38gamma. We presume that the p38gamma-PTPN4 interaction promotes cellular signaling preventing cell death induction.

Molecular Basis of The Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-Activated Protein Kinase p38gamma.,Maisonneuve P, Caillet-Saguy C, Vaney MC, Edoo BZ, Sawyer K, Raynal B, Delepierre M, Lafon M, Cordier F, Wolff N J Biol Chem. 2016 May 31. pii: jbc.M115.707208. PMID:27246854^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.