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Article Dans Une Revue Biochemical Journal Année : 2011

Evidence of SHIP2 S132 phosphorylation, its nuclear localization and stability

William'S Elong Edimo
  • Fonction : Auteur
Rita Derua
  • Fonction : Auteur
Veerle Janssens
  • Fonction : Auteur
Takeshi Nakamura
  • Fonction : Auteur
Jean-Marie Vanderwinden
  • Fonction : Auteur
Etienne Waelkens
  • Fonction : Auteur
Christophe Erneux
  • Fonction : Auteur correspondant
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Résumé

PI(3,4,5)P3 and PI(3,4)P2 are major signalling molecules in mammalian cell biology. PI(3,4)P2 can be produced by PI 3-kinases but also by PI 5-phosphatases including SHIP2. Proteomic studies in human cells revealed that SHIP2 can be phosphorylated at more than 20 sites but their individual function is unknown. In a model of PTEN-null astrocytoma cells, lowering SHIP2 expression leads to increased PI(3,4,5)P3 levels and Akt phosphorylation. Mass spec analysis identified SHIP2 phosphosites on S132, T1254 and S1258; phosphotyrosine containing sites were undetectable. By immunostaining, total SHIP2 concentrated in the perinuclear area and in the nucleus, while phospho SHIP2 S132 was in the cytoplasm, the nucleus and nuclear speckles depending on the cell cycle. SHIP2 phosphorylated on S132 demonstrated PI(4,5)P2 phosphatase activity. Endogenous phospho SHIP2 S132 showed an overlap with PI(4,5)P2 staining in nuclear speckles. SHIP2 S132A was less sensitive to C-terminal degradation and more resistant to calpain as compared to wild type enzyme. We have identified nuclear lamin A/C as a novel SHIP2 interactor. We suggest that the function of SHIP2 is different at the plasma membrane where it recognizes PI(3,4,5)P3 and in the nucleus where it may interact with PI(4,5)P2, particularly in speckles.

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Dates et versions

hal-00633600 , version 1 (19-10-2011)

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William'S Elong Edimo, Rita Derua, Veerle Janssens, Takeshi Nakamura, Jean-Marie Vanderwinden, et al.. Evidence of SHIP2 S132 phosphorylation, its nuclear localization and stability. Biochemical Journal, 2011, 439 (3), pp.391-401. ⟨10.1042/BJ20110173⟩. ⟨hal-00633600⟩

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