ArticleMolecular and cellular biology2000
5' phospholipid phosphatase SHIP-2 causes protein kinase B inactivation and cell cycle arrest in glioblastoma cells.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 185 citations in OpenAlex.
- SHIP2-PLK1 crosstalk promotes sensitivity to dual inhibition in esophageal squamous cell carcinoma.Molecular cancer · 2025Article
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- A spatially organizedScience advances · 2025Article
- Article
- LINC01468 drives NAFLD-HCC progression through CUL4A-linked degradation of SHIP2.Cell death discovery · 2022Article
- Reversely immortalized mouse salivary gland cells presented a promising metabolic and fibrotic response upon BMP9/Gdf2 stimulation.Cellular & molecular biology letters · 2022Article
- When PIPFrontiers in cell and developmental biology · 2022Review
- PTEN and Other PtdIns(3,4,5)PInternational journal of molecular sciences · 2020Review
- YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA.Cell death & disease · 2020Article
- Endothelial dysfunction due to selective insulin resistance in vascular endothelium: insights from mechanistic modeling.American journal of physiology. Endocrinology and metabolism · 2020 · on this mapArticle
- IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity.International journal of molecular sciences · 2020Article
- Article
- Structural basis for interdomain communication in SHIP2 providing high phosphatase activity.eLife · 2017Article
- PI(3,4)PCancer science · 2017Article
- Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells.International journal of molecular sciences · 2017Article
- Suppression of SHIP2 contributes to tumorigenesis and proliferation of gastric cancer cells via activation of Akt.Journal of gastroenterology · 2016Article
- Phosphatidylinositolphosphate phosphatase activities and cancer.Journal of lipid research · 2016Review
- Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate.International journal of endocrinology · 2016Review
- Article
- Discovery and development of small molecule SHIP phosphatase modulators.Medicinal research reviews · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The tumor suppressor protein PTEN is mutated in glioblastoma multiform brain tumors, resulting in deregulated signaling through the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB) pathway, which is critical for maintaining proliferation and survival. We have examined the relative roles of the two major phospholipid products of PI3K activity, phosphatidylinositol 3,4-biphosphate [PtdIns(3,4)P2] and phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3], in the regulation of PKB activity in glioblastoma cells containing high levels of both of these lipids due to defective PTEN expression. Reexpression of PTEN or treatment with the PI3K inhibitor LY294002 abolished the levels of both PtdIns(3, 4)P2 and PtdIns(3,4,5)P3, reduced phosphorylation of PKB on Thr308 and Ser473, and inhibited PKB activity. Overexpression of SHIP-2 abolished the levels of PtdIns(3,4,5)P3, whereas PtdIns(3,4)P2 levels remained high. However, PKB phosphorylation and activity were reduced to the same extent as they were with PTEN expression. PTEN and SHIP-2 also significantly decreased the amount of PKB associated with cell membranes. Reduction of SHIP-2 levels using antisense oligonucleotides increased PKB activity. SHIP-2 became tyrosine phosphorylated following stimulation by growth factors, but this did not significantly alter its phosphatase activity or ability to antagonize PKB activation. Finally we found that SHIP-2, like PTEN, caused a potent cell cycle arrest in G(1) in glioblastoma cells, which is associated with an increase in the stability of expression of the cell cycle inhibitor p27(KIP1). Our results suggest that SHIP-2 plays a negative role in regulating the PI3K-PKB pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.