ArticleCancer research2010
Phosphorylation of RalB is important for bladder cancer cell growth and metastasis.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- RalB promotes lymph node metastasis in tongue squamous cell carcinoma.Genes & genomics · 2025Article
- RalB uncoupling from exocyst is required for endothelial Weibel-Palade body exocytosis.Molecular biology of the cell · 2025Article
- Identification of RAS-like oncoprotein B (RALB) as a potential prognostic and therapeutic target in head and neck squamous cell carcinoma.American journal of translational research · 2024Article
- Review
- Mini-review: Recent advances in post-translational modification site prediction based on deep learning.Computational and structural biotechnology journal · 2022Review
- Review
- PHLPPing the balance: restoration of protein kinase C in cancer.The Biochemical journal · 2021Review
- A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients' Omics Signatures.Cancers · 2020Article
- A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization.International journal of molecular sciences · 2020Review
- RalA and RalB relocalization to depolarized mitochondria depends on clathrin-mediated endocytosis and facilitates TBK1 activation.PloS one · 2019Article
- Glycogen debranching enzyme (AGL) is a novel regulator of non-small cell lung cancer growth.Oncotarget · 2018Article
- RAL GTPases: Biology and Potential as Therapeutic Targets in Cancer.Pharmacological reviews · 2018Review
- Ral signaling pathway in health and cancer.Cancer medicine · 2017Review
- Understanding the biology of urothelial cancer metastasis.Asian journal of urology · 2016Review
- Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.Cellular signalling · 2016Article
- Inhibition of Ral GTPases Using a Stapled Peptide Approach.The Journal of biological chemistry · 2016Article
- The miR-130 family promotes cell migration and invasion in bladder cancer through FAK and Akt phosphorylation by regulating PTEN.Scientific reports · 2016Article
- Divergent roles of CAAX motif-signaled posttranslational modifications in the regulation and subcellular localization of Ral GTPases.The Journal of biological chemistry · 2015Article
- Involvement of RalB in the effect of geranylgeranyltransferase I on glioma cell migration and invasion.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
RalA and RalB are monomeric G proteins that are 83% identical in amino acid sequence but have paralogue-specific effects on cell proliferation, metastasis, and apoptosis. Using in vitro kinase assays and phosphosite-specific antibodies, here we show phosphorylation of RalB by protein kinase C (PKC) and RalA by protein kinase A. We used mass spectrometry and site-directed mutagenesis to identify S198 as the primary PKC phosphorylation site in RalB. Phorbol ester [phorbol 12-myristate 13-acetate (PMA)] treatment of human bladder carcinoma cells induced S198 phosphorylation of stably expressed FLAG-RalB as well as endogenous RalB. PMA treatment caused RalB translocation from the plasma membrane to perinuclear regions in a S198 phosphorylation-dependent manner. Using RNA interference depletion of RalB followed by rescue with wild-type RalB or RalB(S198A) as well as overexpression of wild-type RalB or RalB(S198A) with and without PMA stimulation, we show that phosphorylation of RalB at S198 is necessary for actin cytoskeletal organization, anchorage-independent growth, cell migration, and experimental lung metastasis of T24 or UMUC3 human bladder cancer cells. In addition, UMUC3 cells transfected with a constitutively active RalB(G23V) exhibited enhanced subcutaneous tumor growth, whereas those transfected with phospho-deficient RalB(G23V-S198A) were indistinguishable from control cells. Our data show that RalA and RalB are phosphorylated by different kinases, and RalB phosphorylation is necessary for in vitro cellular functions and in vivo tumor growth and metastasis.
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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 OpenQuestion graph.