PTEN Associates with the Vault Particles in HeLa Cells
PTEN is a tumor suppressor that primarily dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to down-regulate the phosphoinositide 3-kinase/Akt signaling pathway. Although the cellular functions of PTEN as a tumor suppressor have been well characterized, the mechanism by which PTEN activity i...
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Veröffentlicht in: | The Journal of biological chemistry 2002-10, Vol.277 (43), p.40247-40252 |
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Sprache: | eng |
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Zusammenfassung: | PTEN is a tumor suppressor that primarily dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to down-regulate the phosphoinositide
3-kinase/Akt signaling pathway. Although the cellular functions of PTEN as a tumor suppressor have been well characterized,
the mechanism by which PTEN activity is modulated by other signal molecules in vivo remains poorly understood. In searching for potential PTEN modulators through protein-protein interaction, we identified
the major vault protein (MVP) as a dominant PTEN-binding protein in a yeast two-hybrid screen. MVP is the major structural
component of vault, the largest intracellular ribonucleoprotein particle. Co-immunoprecipitation confirmed the interaction
between PTEN and MVP in transfected mammalian cells. More importantly, we found that a significant portion of endogenous PTEN
associates with vault particles in human HeLa cells. Deletion mutation analysis demonstrated that MVP binds to the C2 domain
of PTEN and that PTEN interacts with MVP through its EF hand-like motif. Furthermore, the in vitro binding experiments revealed that the interaction of PTEN with MVP is Ca 2+ -dependent. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M207608200 |