ArticleThe Journal of biological chemistry2008
Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Cancer-AssociatedInternational journal of medical sciences · 2025Review
- The Role of Akt/Rab5A Signalling in Regulating Cell Migration of MDA-MB-231 Breast Cancer Cell Line.Archives of Razi Institute · 2023Article
- Article
- Class IA PI3K regulatory subunits: p110-independent roles and structures.Biochemical Society transactions · 2020Review
- The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways.Biochemistry research international · 2020Review
- Focal adhesion kinase-dependent activation of the early endocytic protein Rab5 is associated with cell migration.The Journal of biological chemistry · 2019Article
- Isoform-specific activities of the regulatory subunits of phosphatidylinositol 3-kinases - potentially novel therapeutic targets.Expert opinion on therapeutic targets · 2018Review
- Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation.Scientific reports · 2018Article
- Targeting phosphoinositide 3-kinase (PI3K) in head and neck squamous cell carcinoma (HNSCC).Cancers of the head & neck · 2018Review
- Identification of the Binding Sites on Rab5 and p110beta Phosphatidylinositol 3-kinase.Scientific reports · 2017Article
- Domain analysis reveals striking functional differences between the regulatory subunits of phosphatidylinositol 3-kinase (PI3K), p85α and p85β.Oncotarget · 2017Article
- Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent Roles of PI3K.Frontiers in endocrinology · 2017Review
- Role of p85α in neutrophil extra- and intracellular reactive oxygen species generation.Oncotarget · 2016Article
- Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases.Nature reviews. Rheumatology · 2016Review
- A novel caveolin-1/p85α/Rab5/Tiam1/Rac1 signaling axis in tumor cell migration and invasion.Communicative & integrative biology · 2014Article
- Vinculin and Rab5 complex is required [correction of requited]for uptake of Staphylococcus aureus and interleukin-6 expression.PloS one · 2014Article
- Article
- CREB3L1 is a metastasis suppressor that represses expression of genes regulating metastasis, invasion, and angiogenesis.Molecular and cellular biology · 2013Article
- A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis.Nature reviews. Cancer · 2013Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rab proteins regulate vesicle fusion events during the endocytosis, recycling, and degradation of activated receptor tyrosine kinases. The p85alpha subunit of phosphatidylinositol 3-kinase has GTPase-activating protein activity toward Rab5 and Rab4, an activity severely reduced by a single point mutation (p85-R274A). Expression of p85-R274A resulted in increased platelet-derived growth factor receptor (PDGFR) activation and downstream signaling (Akt and MAPK) and in decreased PDGFR degradation. We now report that the biological consequences of p85-R274A expression cause cellular transformation as determined by the following: aberrant morphological phenotype, loss of contact inhibition, growth in soft agar, and tumor formation in nude mice. Immunohistochemistry shows that the tumors contain activated PDGFR and high levels of activated Akt. Coexpression of a dominant negative Rab5-S34N mutant attenuated these transformed properties. Our results demonstrate that disruption of the RabGAP function of p85alpha due to a single point mutation (R274A) is sufficient to cause cellular transformation via a phosphatidylinositol 3-kinase-independent mechanism partially reversed by Rab5-S34N expression. This critical new role for p85 in the regulation of Rab function suggests a novel role for p85 in controlling receptor signaling and trafficking through its effects on Rab GTPases.
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What OpenQuestion holds
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 OpenQuestion graph.