SHIP-2 and PTEN Are Expressed and Active in Vascular Smooth Muscle Cell Nuclei, but Only SHIP-2 Is Associated with Nuclear Speckles

Déléris, Paul; Bacqueville, Daniel; Gayral, Stéphanie; Carrez, Laurent; Salles, Jean‐Pierre; Fougère, Bertrand; Breton-Douillon, Monique

doi:10.1074/jbc.m300816200

Cited by 83 publications

(61 citation statements)

References 52 publications

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“…5B), it is not a product of the nuclear inositol polyphosphate multikinase that has been reported to exhibit wortmannininsensitive PI 3-kinase activity (Resnick et al, 2005). It is, however, compatible with the well-documented intra-nuclear occurrence of Type I PI 3-kinases (Kim, 1998;Lu et al, 1998;Martelli et al, 2000;Metjian et al, 1999), a regulatory GTPase called PIKE (Ye, 2006), PtdIns(3,4,5)P 3 -specific phosphatases, SHIP2 and PTEN (Deleris et al, 2003), as well as the substrate lipid, PtdIns(4,5)P 2 .…”

Section: Journal Of Cell Science 119 (24)mentioning

confidence: 51%

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Lindsay

McCoull

Davidson

et al. 2006

Journal of Cell Science

124

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Phosphatidylinositol (3,4,5) trisphosphate [PtdIns(3,4,5)P3] is a lipid second messenger, produced by Type I phosphoinositide 3-kinases (PI 3-kinases), which mediates intracellular responses to many growth factors. Although PI 3-kinases are implicated in events at both the plasma membrane and intracellular sites, including the nucleus, direct evidence for the occurrence of PtdIns(3,4,5)P3 at non-plasma membrane locations is limited. We made use of the pleckstrin homology (PH) domain of general receptor for phosphoinositides (Grp1) to detect PtdIns(3,4,5)P3 in an on-section labeling approach by quantitative immunogold electron microscopy. Swiss 3T3 cells contained low levels of PtdIns(3,4,5)P3 that increased up to 15-fold upon stimulation with platelet-derived growth factor (PDGF). The signal was sensitive to PI 3-kinase inhibitors and present mainly at plasma membranes, including lamellipodia, and in a surprisingly large pool within the nuclear matrix. Comparatively little labeling was observed in endomembranes. A similar distribution of PtdIns(3,4,5)P3 was observed in U87MG cells, which lack the PtdIns(3,4,5)P3 phosphatase, PTEN. Re-expression of PTEN into U87MG cells ablated plasma membrane PtdIns(3,4,5)P3, but not the nuclear pool of this lipid even when PTEN was targeted to nuclei. These data have important implications for the versatility of PI 3-kinase signaling and for the proposed functions of PTEN in the nucleus.

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Section: Journal Of Cell Science 119 (24)mentioning

confidence: 51%

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Lindsay

McCoull

Davidson

et al. 2006

Journal of Cell Science

124

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“…PLC-β1 has been reported to localize to nuclear speckles, together with PIP kinases, PIP2, diacylglycerol kinase θ (DGK θ), PLC-δ4, PI 3-Kinase C2α, phosphatase and tension homologue deleted on chromosome 10 (PTEN) and SH2-domain containing inositol phosphatase 2 (SHIP2) (67)(68)(69). It has been demonstrated an association between PLC-β1 and both DGK ζ and PIP Kinase α, in immunoprecipitation experiments with a PLC-β1 specific antibody.…”

Section: Plc-β Isozymesmentioning

confidence: 99%

Multiple roles of phosphoinositide-specific phospholipase C isozymes

Suh¹,

Park²,

Manzoli³

et al. 2008

BMB Reports

447

482

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“…Active PTEN purified from vascular smooth muscle cell nuclei dephosphorylated PIP3, and nuclei from NGF-treated PC12 cells incubated with PTEN showed increased apoptotic DNA fragmentation inhibited by PIP3. 38,39 Moreover, apoptotic stimulation augmented nuclear accumulation of PTEN, and overexpression of catalytically active nuclear PTEN enhanced cell apoptotic responses in U87MG and HEK293 cells. 13 Thus, nuclear PTEN may exert distinct phosphatase activitydependent functions related with its tumour suppressor function, including pro-apoptotic functions, which are likely to be cell type and cell differentiation specific.…”

mentioning

confidence: 99%

Nuclear PTEN: a tale of many tails

Gil

Andrés-Pons²,

Pulido³

2006

Cell Death Differ

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The PTEN tumour suppressor is one of the more commonly inactivated proteins in human cancer and a key regulator of the PI3K/Akt survival pathway. Its direct involvement in human disease, as well as its important role in many cellular processes, including cell development and differentiation, cell growth, apoptosis, cell motility, cell size, stem cell survival, and longevity, has made PTEN the focus of attention of many researchers and clinicians. The major biological function of PTEN resides in its phosphatase activity towards the lipid second messenger phosphatydilinositol-3,4,5-triphosphate (PIP3), antagonizing the activity of the PI3K oncoproteins, and the association of PTEN to lipids at the plasma membrane is required to exert this function. [1][2][3] In addition, the presence of PTEN in the nucleus of many different cell types, and the finding of unexpected PTEN functions in the nucleus has revealed that the regulation of its nuclear/cytoplasmic distribution may also be a key mechanism to drive PTEN functions.4-6 Here, we discuss the current models to explain the regulation of PTEN nuclear accumulation, and the molecular linkage between the targeting of PTEN to the nucleus and to lipid membranes. The distinct pathways that mediate nuclear PTEN functions in the control of cell growth and apoptosis are also discussed. Molecular Mechanisms of PTEN Nuclear AccumulationThe tumour suppressor PTEN protein is present in the nucleus of different cell types, including cell lines and tissue cells.7-10 However, PTEN amino-acid sequence lacks obvious canonical nuclear localization signal sequences (NLS) or nuclear export sequences (NES) that could account for the targeting of the protein in or out of the nucleus, making elusive the molecular basis of PTEN nuclear/cytoplasmic distribution. Recent findings, however, suggest that PTEN entry and accumulation in the nucleus may be controlled by a variety of mechanisms. Chung et al.11 have reported that, in the MCF-7 breast carcinoma cell line, PTEN may be transported into the nucleus using several putative NLS-like sequences located in the PTP and the C2 domains of the protein. Mutating such NLS-like sequences individually did not affect PTEN nuclear/ cytoplasmic distribution. However, combined mutations of the NLS-like sequences caused defective PTEN nuclear accumulation. Based on the differential interaction of the major vault protein (MVP) with wild-type PTEN and with the NLS-like mutants, as well as on the nuclear localization pattern of MVP, the authors propose a model of PTEN nuclear import mediated by MVP. Interestingly, PTEN was found in this study to interact with importin a and b proteins, although such interaction was also observed in the NLS-like mutants that displayed defective nuclear accumulation. A second model of PTEN nuclear entry has been proposed by Liu et al.12 Using PTEN fusion proteins of variable size, the authors of this study noticed that large PTEN fusion proteins (4100 kDa) did not show nuclear localization, whereas PTEN alone (47 kDa) or a GFP-P...

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SHIP-2 and PTEN Are Expressed and Active in Vascular Smooth Muscle Cell Nuclei, but Only SHIP-2 Is Associated with Nuclear Speckles

Cited by 83 publications

References 52 publications

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Multiple roles of phosphoinositide-specific phospholipase C isozymes

Nuclear PTEN: a tale of many tails

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