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

Mariarosaria Incoronato1, Amelia D'Alessio, Simona Paladino

  • 1Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli "Federico II", Via S. Pansini 5, 80131, Naples, Italy.

Cellular Signalling
|April 30, 2004
PubMed

Insights

Shp-1 and Shp-2 phosphatases interact differently with Ret receptor mutants, influencing cancer syndromes like MEN 2A and 2B. Their distinct complexes within and outside lipid rafts mediate varied biological functions.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Genetics

Background:

  • The Ret receptor tyrosine kinase is crucial for development and implicated in cancers.
  • Shp-1 and Shp-2 phosphatases modulate Ret signaling pathways.
  • Mutations in Ret cause Multiple Endocrine Neoplasia (MEN) types 2A and 2B.

Purpose of the Study:

  • To investigate the distinct interactions of Shp-1 and Shp-2 with activated Ret mutants.
  • To determine how these interactions affect downstream signaling and cellular localization.
  • To elucidate the role of phosphatases in Ret-mediated oncogenesis.

Main Methods:

  • Utilized rat pheochromocytoma-derived PC12 cells.
  • Studied interactions with Ret(C634Y) and Ret(M918T) mutants.
  • Analyzed protein complex formation and localization within lipid rafts.

Main Results:

  • Both Shp-1 and Shp-2 associate with Ret mutants in distinct multiprotein complexes.
  • Shp-1-Ret and Shp-2-Ret complexes exhibit differential localization inside and outside lipid rafts.
  • Activated Ret proteins do not directly bind to or act as substrates for Shp-1 or Shp-2.

Conclusions:

  • Ret complexes within and outside lipid rafts mediate distinct biological functions.
  • The presence and type of Shp phosphatases contribute to determining these functions.
  • Understanding these interactions is key to deciphering Ret-driven cancer mechanisms.

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