title: The eighth fibronectin type III domain of protein tyrosine phosphatase receptor J influences the formation of protein complexes and cell localization.
abstract: Regulation of receptor-type phosphatases can involve the formation of higher-order structures, but the exact role played in this process by protein domains is not well understood. In this study we show the formation of different higher-order structures of the receptor-type phosphatase PTPRJ, detected in HEK293A cells transfected with different PTPRJ expression constructs. In the plasma membrane PTPRJ forms dimers detectable by treatment with the cross-linking reagent BS(3) (bis[sulfosuccinimidyl]suberate). However, other PTPRJ complexes, dependent on the formation of disulfide bonds, are detected by treatment with the oxidant agent H(2)O(2) or by a mutation Asp872Cys, located in the eighth fibronectin type III domain of PTPRJ. A deletion in the eighth fibronectin domain of PTPRJ impairs its dimerization in the plasma membrane and increases the formation of PTPRJ complexes dependent on disulfide bonds that remain trapped in the cytoplasm. The deletion mutant maintains the catalytic activity but is unable to carry out inhibition of proliferation on HeLa cells, achieved by the wild type form, since it does not reach the plasma membrane. Therefore, the intact structure of the eighth fibronectin domain of PTPRJ is critical for its localization in plasma membrane and biological function.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia, Università di Catanzaro, 88100 Catanzaro, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Iuliano
authors.forename: Cinzia
authors.initials: C
authors.lastname: Raso
authors.forename: Alfina
authors.initials: A
authors.lastname: Quintiero
authors.forename: Ilaria Le
authors.initials: IL
authors.lastname: Pera
authors.forename: Flavia
authors.initials: F
authors.lastname: Pichiorri
authors.forename: Tiziana
authors.initials: T
authors.lastname: Palumbo
authors.forename: Dario
authors.initials: D
authors.lastname: Palmieri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pattarozzi
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viglietto
authors.forename: Francesco
authors.initials: F
authors.lastname: Trapasso
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Croce
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004220:Disulfides / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry*; D006801:Humans; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000737:chemistry* / Q000378:metabolism*; D017384:Sequence Deletion / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D004220:Disulfides; D005353:Fibronectins; D046912:Multiprotein Complexes; D050505:Mutant Proteins; D016877:Oxidants; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3