ArticleScientific reports2015
PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Driver or passenger? A new assessment of genes in the schizophrenia-associated 3q29 deletion locus for contribution to neurodevelopmental disorders.Journal of neurodevelopmental disorders · 2026Review
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Article
- Tyrosine Kinase Inhibitors Diminish Renal Neoplasms in a Tuberous Sclerosis Model Via Induction of Apoptosis.Molecular cancer therapeutics · 2023Article
- Induction by rapamycin and proliferation‑promoting activity of Hspb1 in aExperimental and therapeutic medicine · 2023Article
- The molecular athlete: exercise physiology from mechanisms to medals.Physiological reviews · 2023Review
- Specific Features of Focal Cortical Dysplasia in Tuberous Sclerosis Complex.Current issues in molecular biology · 2023Review
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Nischarin Deletion Reduces Oxidative Metabolism and Overall ATP: A Study Using a NovelInternational journal of molecular sciences · 2022Article
- PAK3 is a key signature gene of the glioma proneural subtype and affects its proliferation, differentiation and growth.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Targeting the complex I and III of mitochondrial electron transport chain as a potentially viable option in liver cancer management.Cell death discovery · 2021Article
- Rapamycin and dexamethasone during pregnancy prevent tuberous sclerosis complex-associated cystic kidney disease.JCI insight · 2020Article
- Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients.Journal of clinical medicine · 2019Article
- Kinase activity is impaired in neutrophils of sepsis patients.Haematologica · 2019Article
- Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.Experimental neurobiology · 2019Article
- Curcumin and resveratrol suppress dextran sulfate sodium‑induced colitis in mice.Molecular medicine reports · 2019Article
- Human mesenchymal stromal cells in adhesion to cell-derived extracellular matrix and titanium: Comparative kinome profile analysis.Journal of cellular physiology · 2019Article
- The Human Cytomegalovirus UL38 protein drives mTOR-independent metabolic flux reprogramming by inhibiting TSC2.PLoS pathogens · 2019Article
- The mTOR Independent Function of Tsc1 and FNIPs.Trends in biochemical sciences · 2018Article
- Peptidoglycan Suppresses Phagocytic Activities and Apoptosis of Macrophages in Colonic Mucosa Tissues of Crohn's Disease Patients and In Vitro.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberous sclerosis complex (TSC) is caused by inactivating mutations in either TSC1 or TSC2 and is characterized by uncontrolled mTORC1 activation. Drugs that reduce mTOR activity are only partially successful in the treatment of TSC, suggesting that mTOR-independent pathways play a role in disease development. Here, kinome profiles of wild-type and Tsc2(-/-) mouse embryonic fibroblasts (MEFs) were generated, revealing a prominent role for PAK2 in signal transduction downstream of TSC1/2. Further investigation showed that the effect of the TSC1/2 complex on PAK2 is mediated through RHEB, but is independent of mTOR and p21RAC. We also demonstrated that PAK2 over-activation is likely responsible for the migratory and cell cycle abnormalities observed in Tsc2(-/-) MEFs. Finally, we detected high levels of PAK2 activation in giant cells in the brains of TSC patients. These results show that PAK2 is a direct effector of TSC1-TSC2-RHEB signaling and a new target for rational drug therapy in TSC.
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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.