title: Isolation and functional characterization of peptide agonists of PTPRJ, a tyrosine phosphatase receptor endowed with tumor suppressor activity.
abstract: PTPRJ is a receptor-type protein tyrosine phosphatase whose expression is strongly reduced in the majority of investigated cancer cell lines and tumor specimens. PTPRJ negatively interferes with mitogenic signals originating from several oncogenic receptor tyrosine kinases, including HGFR, PDGFR, RET, and VEGFR-2. Here we report the isolation and characterization of peptides from a random peptide phage display library that bind and activate PTPRJ. These agonist peptides, which are able to both circularize and form dimers in acqueous solution, were assayed for their biochemical and biological activity on both human cancer cells and primary endothelial cells (HeLa and HUVEC, respectively). Our results demonstrate that binding of PTPRJ-interacting peptides to cell cultures dramatically reduces the extent of both MAPK phosphorylation and total phosphotyrosine levels; conversely, they induce a significant increase of the cell cycle inhibitor p27(Kip1). Moreover, PTPRJ agonist peptides both reduce proliferation and trigger apoptosis of treated cells. Our data indicate that peptide agonists of PTPRJ positively modulate the PTPRJ activity and may lead to novel targeted anticancer therapies.
authors: Dipartimento di Medicina Sperimentale e Clinica, Università "Magna Græcia" di Catanzaro, Campus "S. Venuta", Catanzaro, Italy.
authors: Francesco
authors: F
authors: Paduano
authors: Francesco
authors: F
authors: Ortuso
authors: Pietro
authors: P
authors: Campiglia
authors: Cinzia
authors: C
authors: Raso
authors: Enrico
authors: E
authors: Iaccino
authors: Marco
authors: M
authors: Gaspari
authors: Eugenio
authors: E
authors: Gaudio
authors: Graziella
authors: G
authors: Mangone
authors: Alfonso
authors: A
authors: Carotenuto
authors: Anna
authors: A
authors: Bilotta
authors: Domenico
authors: D
authors: Narciso
authors: Camillo
authors: C
authors: Palmieri
authors: Valter
authors: V
authors: Agosti
authors: Anna
authors: A
authors: Artese
authors: Isabel
authors: I
authors: Gomez-Monterrey
authors: Marina
authors: M
authors: Sala
authors: Giovanni
authors: G
authors: Cuda
authors: Rodolfo
authors: R
authors: Iuliano
authors: Nicola
authors: N
authors: Perrotti
authors: Giuseppe
authors: G
authors: Scala
authors: Giuseppe
authors: G
authors: Viglietto
authors: Stefano
authors: S
authors: Alcaro
authors: Carlo M
authors: CM
authors: Croce
authors: Ettore
authors: E
authors: Novellino
authors: Alfredo
authors: A
authors: Fusco
authors: Francesco
authors: F
authors: Trapasso
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D019151:Peptide Library; D010455:Peptides; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019000:Phosphotyrosine; D020928:Mitogen-Activated Protein Kinases; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3