Regulation of the catalytic activity of the human phosphatase <scp>PTPN</scp>4 by its <scp>PDZ</scp> domain

Maisonneuve, Pierre; Caillet‐Saguy, Célia; Raynal, Bertrand; Gilquin, Bernard; Chaffotte, Alain; Pérez, Javier; Zinn‐Justin, Sophie; Delepierre, Muriel; Buc, Henri; Cordier, Florence; Wolff, Nicolas

doi:10.1111/febs.13024

Cited by 20 publications

(53 citation statements)

References 39 publications

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“…The catalytic activity of both PTPN4 and PTPN3 is autoinhibited by their PDZ domain when the PDZ and PTP two-domain adopt a compact conformation (20,30). We demonstrate here that the binding of the PBM of p38␥ to PTPN4-PDZ lifts this inhibition and restores the PTPN4 phosphatase activity.…”

Section: Discussionmentioning

confidence: 75%

“…The four PTPN4-PDZ subunits are disulfide-bonded by pair: chains A to B and chains C to D for PTPN4-PDZ⅐Cyto8-RETEV structure; chains A to D and chains B to C for PTPN4-PDZ⅐p38␥-KETPL structure. However, the monomeric state of the PDZ domain in complex with these peptides in solution was previously confirmed, implying that the intermolecular disulfide bonds are due to crystalline conditions (15) and (20).…”

Section: Methodsmentioning

confidence: 91%

“…Uniformly 15 N-labeled and non-labeled PTPN4 PDZ, PTP, PDZ-PTP WT , and PDZ-PTP CS constructs were expressed and purified as previously described (20). The unlabeled, 15 N-labeled and 13 C, 2 H, 15 N-labeled p38␥ proteins were purified as previously described (20). PDZ ligands, p38␥-KETPL (SWARVSKETPL) and Cyto8-RETEV (SWESHKSGRETEV), were synthesized in solid phase using Fmoc (N-(9-fluorenyl)methoxycarbonyl) strategy (Proteogenix).…”

Section: Methodsmentioning

confidence: 99%

“…Phosphatase Assay and Kinetic Analysis-Phosphatase activity with phosphopeptides and p-nitrophenyl phosphate was measured as previously described (20). Reactions were measured with various phosphopeptide pTGpY concentrations ranging from 1.8 M to 225 M at an enzyme concentration of 10 nM.…”

Section: Methodsmentioning

confidence: 99%

“…The Inhibition of the Catalytic Activity of PTPN4 by Its PDZ Domain Is Released when the PDZ Binding Site Is Occupied by p38␥-KETPL-We recently demonstrated that the PDZ domain of PTPN4 down-regulates the phosphatase activity through intramolecular interactions and that the mere binding of a PDZ ligand releases this catalytic inhibition (20). Here, we investigated whether the binding of p38␥-KETPL to the PDZ domain could also affect this catalytic regulation and in turn modulate the phosphatase activity.…”

mentioning

confidence: 97%

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Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ

Maisonneuve

Caillet‐Saguy

Vaney

et al. 2016

Journal of Biological Chemistry

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The human protein tyrosine phosphatase non-receptor type 4 (PTPN4) prevents cell death induction in neuroblastoma and glioblastoma cell lines in a PDZ⅐PDZ binding motifs-dependent manner, but the cellular partners of PTPN4 involved in cell protection are unknown. Here, we described the mitogen-activated protein kinase p38␥ as a cellular partner of PTPN4. The main contribution to the p38␥⅐PTPN4 complex formation is the tight interaction between the C terminus of p38␥ and the PDZ domain of PTPN4. We solved the crystal structure of the PDZ domain of PTPN4 bound to the p38␥ C terminus. We identified the molecular basis of recognition of the C-terminal sequence of p38␥ that displays the highest affinity among all endogenous partners of PTPN4. We showed that the p38␥ 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 p38␥ to PTPN4 abolishes the catalytic autoinhibition of PTPN4 and thus activates the phosphatase, which can efficiently dephosphorylate the activation loop of p38␥. We presume that the p38␥⅐PTPN4 interaction promotes cellular signaling, preventing cell death induction. PTPN45 is a non-receptor-tyrosine phosphatase (PTP) with functions in T cell signaling, learning, spatial memory, and cerebellar synaptic plasticity (1-3). Its overexpression reduces cell proliferation in COS-7 cells and suppresses CrkI-mediated cell growth and mobility in HEK293T cells (4, 5). PTPN4 also regulates neuronal cell homeostasis by protecting neurons against apoptosis (5, 6). PTPN4 is a large modular protein containing three domains, an N-terminal FERM domain, a PDZ domain, and a C-terminal catalytic tyrosine phosphatase domain (7). PDZ domains are protein-protein interaction domains, which play a central role in cell signaling by favoring spatial contacts between enzymes and their substrates or, more generally, by assembling and/or regulating protein networks (8, 9). Thus, disrupting the interactions between PDZ domains and PDZ binding motifs (PBM) can trigger profound alterations in cell signaling pathways (10 -12). Such disruptions of PDZ⅐PBM complexes are used by viruses to hijack cell signaling pathways to their own advantage and can also be obtained by treating cells with an excess of cell penetrating peptide encoding a PBM (13). Indeed, we showed that rabies virus (RABV) peptides encoding a PBM can target the PDZ domain of PTPN4 (PTPN4-PDZ) and antagonize the function of PTPN4, leading to cell death (6). We optimized such pro-apoptotic peptides and designed the Cyto8-RETEV sequence, that is so far the most affine ligand of PTPN4-PDZ and the best inducer of cell death (15).Four endogenous partners of PTPN4 have been reported: the glutamate receptor ␦2 and ⑀ subunits, the T-cell receptor subunit, the CrkI oncoprotein, and the TRIF (TIR domain-containing adaptor-inducing interferon-B)-related adaptor molecule TRAM (3,5,16,17). Nevertheless, the natural ligands of PTPN4 involved in the regulation of cell homeos...

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Section: Discussionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 97%

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Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ

Maisonneuve

Caillet‐Saguy

Vaney

et al. 2016

Journal of Biological Chemistry

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A Successful Combination: Coupling SE-HPLC with SAXS

Pérez¹,

Vachette²

2017

Advances in Experimental Medicine and Biology

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A monodispersed and ideal solution is a central (unique?) requirement of SAXS to allow one to extract structural information from the recorded pattern. On-line Size Exclusion Chromatography (SEC) marked a major breakthrough, separating particles present in solution according to their size. Identical frames under an elution peak can be averaged and further processed free from contamination. However, this is not always straightforward, separation is often incomplete and software have been developed to deconvolve the contributions from the different species (molecules or oligomeric forms) within the sample. In this chapter, we present the general workflow of a SEC-SAXS experiment. We present recent instrumental and data analysis improvements that have improved the quality of recorded data, extended its potential and turn it into a mainstream approach. We describe into some details two specific applications of SEC-SAXS that provide more than just separating associated forms from the particle of interest.

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1H, 13C and 15N backbone resonance assignments and dynamic properties of the PDZ tandem of Whirlin

2016

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Mammals perceive sounds thanks to mechanosensory hair cells located in the inner ear. The stereocilia of these cells are tightly bound together in bundles by a network of cadherins and scaffolding proteins. Stereocilia deflection induces stretching of this network and is responsible for hair cell depolarization that triggers the neuronal message, transducing the mechanical signal into an electric signal transmissible to the brain. Nearly all proteins involved in this mechano-electrical transduction network contain short C-terminal motifs of interaction with PDZ domains (PSD-95, Discs Large, ZO-1). Interestingly only two of these proteins encompass PDZ domains: Harmonin and Whirlin. As our first step towards a comprehensive structural study of Whirlin, we have assigned the (1)H, (13)C and (15)N backbone resonances of a tandem formed by the first two PDZ domains of Whirlin, reported the secondary structure elements of this tandem as predicted by the TALOS+ server and evaluated its dynamics from (15)N relaxation measurements.

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Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain

Cited by 20 publications

References 39 publications

Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ

Molecular Basis of the Interaction of the Human Protein Tyrosine Phosphatase Non-receptor Type 4 (PTPN4) with the Mitogen-activated Protein Kinase p38γ

A Successful Combination: Coupling SE-HPLC with SAXS

1H, 13C and 15N backbone resonance assignments and dynamic properties of the PDZ tandem of Whirlin

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