The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes

Mariarosaria Incoronato, Amelia D'Alessio, Simona Paladino, Chiara Zurzolo, Maria Stella Carlomagno, Laura Cerchia, Vittorio De Franciscis

Research output: Contribution to journalArticlepeer-review

Abstract

The Shp-2 and Shp-1 non-transmembrane tyrosine phosphatases display different and even opposing effects on downstream signaling events initiated by Ret activation. By using rat pheochromocytoma-derived PC12 cells, here we studied the interactions of Shp-2 and Shp-1 with two activated mutants of Ret receptor, RetC634Y and RetM918T. Each of these mutated receptors causes inheritance of distinct cancer syndromes, multiple endocrine neoplasia (MEN) type 2A and type 2B, respectively. We show that: (i) both Shp-1 and Shp-2 are associated to a multiprotein complex that includes Ret mutants; (ii) the Shp-1-Ret complexes are distinct from Shp-2-Ret complexes, and these complexes are differently distributed inside and outside lipid rafts; (iii) constitutively activated Ret proteins neither directly bind to nor are substrates of these phosphatases. Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions.

Original languageEnglish
Pages (from-to)847-856
Number of pages10
JournalCellular Signalling
Volume16
Issue number7
DOIs
Publication statusPublished - Jul 2004

Keywords

  • GDNF
  • glial cell line-derived neurotrophic factor
  • glutathione S-transferase
  • GST
  • Lipid rafts
  • MEN
  • MEN2
  • multiple endocrine neoplasia
  • Oncogene
  • PC12
  • Ret
  • SH2-containing tyrosine phosphatase 1
  • SH2-containing tyrosine phosphatase 2
  • Shp-1
  • Shp-2

ASJC Scopus subject areas

  • Cell Biology

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