title: Phosphotyrosine phosphatase R3 receptors: Origin, evolution and structural diversification.
abstract: Subtype R3 phosphotyrosine phosphatase receptors (R3 RPTPs) are single-spanning membrane proteins characterized by a unique modular composition of extracellular fibronectin repeats and a single cytoplasmatic protein tyrosine phosphatase (PTP) domain. Vertebrate R3 RPTPs consist of five members: PTPRB, PTPRJ, PTPRH and PTPRO, which dephosphorylate tyrosine residues, and PTPRQ, which dephosphorylates phophoinositides. R3 RPTPs are considered novel therapeutic targets in several pathologies such as ear diseases, nephrotic syndromes and cancer. R3 RPTP vertebrate receptors, as well as their known invertebrate counterparts from animal models: PTP52F, PTP10D and PTP4e from the fruitfly Drosophila melanogaster and F44G4.8/DEP-1 from the nematode Caenorhabditis elegans, participate in the regulation of cellular activities including cell growth and differentiation. Despite sharing structural and functional properties, the evolutionary relationships between vertebrate and invertebrate R3 RPTPs are not fully understood. Here we gathered R3 RPTPs from organisms covering a broad evolutionary distance, annotated their structure and analyzed their phylogenetic relationships. We show that R3 RPTPs (i) have probably originated in the common ancestor of animals (metazoans), (ii) are variants of a single ancestral gene in protostomes (arthropods, annelids and nematodes); (iii) a likely duplication of this ancestral gene in invertebrate deuterostomes (echinodermes, hemichordates and tunicates) generated the precursors of PTPRQ and PTPRB genes, and (iv) R3 RPTP groups are monophyletic in vertebrates and have specific conserved structural characteristics. These findings could have implications for the interpretation of past studies and provide a framework for future studies and functional analysis of this important family of proteins.
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Javier U
authors.initials: JU
authors.lastname: Chicote
authors.affiliation: Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NewYork, United States of America.
authors.forename: Rob
authors.initials: R
authors.lastname: DeSalle
authors.affiliation: Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García-España
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D010802:Phylogeny; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D017027:Protein Tyrosine Phosphatases; C519388:Ptp10D protein, Drosophila; C533524:Ptp4E protein, Drosophila; C442232:Ptp52F protein, Drosophila; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4