Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain. (30th September 2014)

• Record Type: Journal Article
• Authors: Maisonneuve, Pierre; Caillet‐Saguy, Célia; Raynal, Bertrand; Gilquin, Bernard; Chaffotte, Alain; Pérez, Javier; Zinn‐Justin, Sophie; Delepierre, Muriel; Buc, Henri; Cordier, Florence; Wolff, Nicolas
• Is Part Of: FEBS journal. Volume 281:Number 21(2014)
• Page Start: 4852
• Page End: 4865
• Publication Date: 2014-09-30
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13024
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs13024-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="febs13024-sec-0001" sec-type="section"> <p>The human protein tyrosine phosphatase non‐receptor type 4 (PTPN4) prevents cells death. Targeting its PDZ domain abrogates this protection and triggers apoptosis. We demonstrate here that the PDZ domain inhibits the phosphatase activity of PTPN4. The mere binding of a PDZ ligand is sufficient to release the catalytic inhibition. We combined analytical ultracentrifugation, small angle X‐ray scattering and NMR to understand how the PDZ domain controls PTPN4 activity. We show that the physiologically active PTPN4 two‐domain, encompassing the PDZ and the phosphatase domains, adopts a predominant compact conformation in solution. The PDZ ligand binding restores the catalytic competence of PTPN4 disrupting the transient interdomain communication. This study strengthens the emerging notion that PDZ domains can act as regulators of enzyme activity and therefore are active players in the dynamic regulation of signaling pathways.</p> </sec> <sec id="febs13024-sec-0002" sec-type="section"> <title>Structured digital abstract</title> <p> <list id="febs13024-list-0001" list-type="bullet"> <list-item> <p> <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/P29074" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">PTPN4_linker-PTP</ext-link> <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0203" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">dephosphorylates</ext-link> <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/P53778" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">pTyr peptide</ext-link> by <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0415" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enzymatic study</ext-link> (<ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/intact/interaction/EBI-9681788" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">View interaction</ext-link>)</p> </list-item> <list-item> <p> <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/P29074" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">PTPN4_PDZ-PTP</ext-link> <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0203" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">dephosphorylates</ext-link> <ext-link ext-link-type="uri" xlink:href="http://www.uniprot.org/uniprot/P53778" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">pTyr peptide</ext-link> by <ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0415" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">enzymatic study</ext-link> (<ext-link ext-link-type="uri" xlink:href="http://www.ebi.ac.uk/intact/interaction/EBI-9681802" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">View interaction</ext-link>)</p> </list-item> </list> </p> </sec> </abstract>