ArticleOncogene1999
The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 90 citations in OpenAlex.
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- Nerve Growth Factor Induces Proliferation and Aggressiveness In Prostate Cancer Cells.Cancers · 2019Article
- Overexpression of SMN2 Gene in Motoneuron-Like Cells Differentiated from Adipose-Derived Mesenchymal Stem Cells by Ponasterone A.Journal of molecular neuroscience : MN · 2019Article
- TRKing down an old oncogene in a new era of targeted therapy.Cancer discovery · 2015Review
- Forkhead family transcription factor FoxO and neural differentiation.Neurogenetics · 2012Review
- Article
- Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function.Journal of biomedical science · 2010Article
- Involvement of Akt in neurite outgrowth.Cellular and molecular life sciences : CMLS · 2009Review
- A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth.Journal of neuroscience research · 2009Article
- Multiple Gi proteins participate in nerve growth factor-induced activation of c-Jun N-terminal kinases in PC12 cells.Neurochemical research · 2009Article
- Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- The protein phosphatase 2A regulatory subunits B'beta and B'delta mediate sustained TrkA neurotrophin receptor autophosphorylation and neuronal differentiation.Molecular and cellular biology · 2009Article
- Cholinergic system during the progression of Alzheimer's disease: therapeutic implications.Expert review of neurotherapeutics · 2008Review
- CTLA-4 activation of phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death.PloS one · 2008Article
- Role of Cdc42 in neurite outgrowth of PC12 cells and cerebellar granule neurons.Molecular and cellular biochemistry · 2006Article
- A novel substrate of receptor tyrosine phosphatase PTPRO is required for nerve growth factor-induced process outgrowth.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
- Role of integrin-linked kinase in nerve growth factor-stimulated neurite outgrowth.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003Article
- Biological activity of the thyroid TRK-T3 oncogene requires signalling through Shc.British journal of cancer · 2002Article
- Phosphorylation of HDM2 by Akt.Oncogene · 2002Article
- GSK3 takes centre stage more than 20 years after its discovery.The Biochemical journal · 2001Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Trk/Nerve Growth Factor receptor mediates the rapid activation of a number of intracellular signaling proteins, including phosphatidylinositol 3-kinase (PI 3-kinase). Here, we describe a novel, NGF-inducible system that we used to specifically address the signaling potential of endogenous PI 3-kinase in NGF-mediated neuronal survival and differentiation processes. This system utilizes a Trk receptor mutant (Trk(def)) lacking sequences Y490, Y785 and KFG important for the activation of the major Trk targets; SHC, PLC-gammal, Ras, PI 3-kinase and SNT. Trk(def) was kinase active but defective for NGF-induced responses when stably expressed in PC12nnr5 cells (which lack detectable levels of TrkA and are non-responsive to NGF). The PI 3-kinase consensus binding site, YxxM (YVPM), was introduced into the insert region within the kinase domain of Trk(def). NGF-stimulated tyrosine phosphorylation of the Trk(def)+PI 3-kinase addback receptor, resulted in the direct association and selective activation of PI 3-kinase in vitro and the production of PI(3,4)P2 and PI(3,4,5)P3 in vivo (comparable to wild-type). PC12nnr5 cells stably expressing Trk(def) + PI 3-kinase, initiated neurite outgrowth but failed to stably extend and maintain these neurites in response to NGF as compared to PC12 parental cells, or PC12nnr5 cells overexpressing wild-type Trk. However, Trk(def) + PI 3-kinase was fully competent in mediating NGF-induced survival processes. We propose that while endogenous PI 3-kinase can contribute in part to neurite initiation processes, its selective activation and subsequent signaling to downstream effectors such as Akt, functions mainly to promote cell survival in the PC12 system.
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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.