Isolation and Functional Characterization of Peptide Agonists of PTPRJ, a Tyrosine Phosphatase Receptor Endowed with Tumor Suppressor Activity
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- 作者：Francesco Paduano ; Francesco Ortuso ; Pietro Campiglia ; Cinzia Raso ; Enrico Iaccino ; Marco Gaspari ; Eugenio Gaudio ; Graziella Mangone ; Alfonso Carotenuto ; Anna Bilotta ; Domenico Narciso ; Camillo Palmieri ; Valter Agosti ; Anna Artese ; Isabel Gomez-Monterrey ; Marina Sala ; Giovanni Cuda ; Rodolfo Iuliano ; Nicola Perrotti ; Giuseppe Scala ; Giuseppe Viglietto ; Stefano Alcaro ; Carlo M. Croce ; Ettore Novellino ; Alfredo Fusco ; Francesco Trapasso
- 刊名：ACS Chemical Biology
- 出版年：2012
- 出版时间：October 19, 2012
- 年：2012
- 卷：7
- 期：10
- 页码：1666-1676
- 全文大小：573K
- 年卷期：v.7,no.10(October 19, 2012)
- ISSN：1554-8937
文摘
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 p27Kip1. 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.