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Journal of Biochemistry Advance Access published online on January 3, 2009
Journal of Biochemistry, doi:10.1093/jb/mvn175
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© The authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

The eighth fibronectin type III domain of Protein Tyrosine Phosphatase Receptor J influences the formation of protein complexes and cell localization

Rodolfo Iuliano*,{dagger}, Cinzia Raso*, Alfina Quintiero*, Ilaria Le Pera*, Flavia Pichiorri{dagger}, Tiziana Palumbo{dagger}, Dario Palmieri{ddagger}, Alessandra Pattarozzi§, Tullio Florio§, Giuseppe Viglietto*, Francesco Trapasso*,{dagger}, Carlo Maria Croce{dagger} and Alfredo Fusco{ddagger},{square},¶

* Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia, Università di Catanzaro, 88100 Catanzaro, Italy.
{dagger} Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, 410 West 12th Avenue, Columbus, Ohio, 43210, USA.
{ddagger} Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II",80131 Napoli, Italy.
§ Sezione Farmacologia, Dipartimento Oncologia, Biologia e Genetica, Università di Genova, 16132 Genova, Italy.
{square} NOGEC (Naples Oncogenomic Center)-CEINGE, Biotecnologie Avanzate, 80145 Napoli, Italy.

¶ To whom correspondence should be addressed: Alfredo Fusco Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II", via Pansini, 5, 80131, Naples, Italy. E-mail: afusco{at}napoli.com

Received October 24, 2008; Accepted December 11, 2008


  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 BS3 (Bis[Sulfosuccinimidyl]suberate). However, other PTPRJ complexes, dependent on the formation of disulfide bonds, are detected by treatment with the oxidant agent H2O2 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.

Key Words: cell localization, disulfide bonds, fibronectin domain, protein complexes, protein tyrosine phosphatase


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