Nuclear Ptdlns(3,4,5)P3 signaling: an ongoing story.

Phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P(3)) is linked to a variety of cellular functions, such as growth, cell survival, and differentiation. Ptdlns(3,4,5)P(3) is primarily synthesized by class I phosphoinositide 3-kinases and its hydrolysis by two 3-phosphoinositide 3-phosphatases, PTEN and SHIP proteins, leads to the production of two other second messengers, Ptdlns(4,5)P(2) and Ptdlns(3,4)P(2), respectively. Evidence accumulated over the last years strongly suggest that Ptdlns(3,4,5)P(3) is an important component of signaling pathway operating within the nucleus. Moreover, recent advances indicated that nuclear translocation of cell surface receptors could activate nuclear phosphoinositide 3-kinase suggesting a new mode of signal transduction. The aim of this review is intended to summarize the state of our knowledge on nuclear Ptdlns(3,4,5)P(3) and its metabolizing enzymes, and to highlight the emerging roles for intranuclear Ptdlns(3,4,5)P(3).