title: PTEN-PDZ domain interactions: binding of PTEN to PDZ domains of PTPN13.
abstract: Protein modular interactions mediated by PDZ domains are essential for the establishment of functional protein networks controlling diverse cellular functions. The tumor suppressor PTEN possesses a C-terminal PDZ-binding motif (PDZ-BM) that is recognized by a specific set of PDZ domains from scaffolding and regulatory proteins. Here, we review the current knowledge on PTEN-PDZ domain interactions and tumor suppressor networks, describe methodology suitable to analyze these interactions, and report the binding of PTEN and the PDZ domain-containing protein tyrosine phosphatase PTPN13. Yeast two-hybrid and GST pull-down analyses showed that PTEN binds to PDZ2/PTPN13 domain in a manner that depends on the specific PTPN13 PDZ domain arrangement involving the interdomain region between PDZ1 and PDZ2. Furthermore, a specific binding profile of PTEN to PDZ2/PTPN13 domain was observed by mutational analysis of the PTEN PDZ-BM. Our results disclose a PDZ-mediated physical interaction of PTEN and PTPN13 with potential relevance in tumor suppression and cell homeostasis.
authors.affiliation: Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Sotelo
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan T G
authors.initials: JT
authors.lastname: Schepens
authors.affiliation: Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Valiente
authors.affiliation: Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wiljan J A J
authors.initials: WJ
authors.lastname: Hendriks
authors.affiliation: Centro de Investigación Príncipe Felipe, Valencia, Spain; BioCruces Health Research Institute, Barakaldo, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. Electronic address: rpulido@gmail.com.
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D054731:PDZ Domains / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D017433:Protein Structure, Secondary; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D025521:Tumor Suppressor Proteins; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: PDZ; PTEN; PTPN13; Protein tyrosine phosphatase; Protein–protein interaction