ArticleOncogene2001
The small-GTPase RalA activates transcription of the urokinase plasminogen activator receptor (uPAR) gene via an AP1-dependent mechanism.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- AP1 Transcription Factor in the Regulation of the Urokinase Plasminogen Activation System.Biomolecules · 2026Review
- uPAR-directed immunotherapies in solid tumors: current advances and future perspectives.Frontiers in pharmacology · 2026Review
- Dysregulation of RalA signaling through dual regulatory mechanisms exerts its oncogenic functions in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2022Article
- Overexpression of Arabidopsis nucleolar GTP-binding 1 (NOG1) proteins confers drought tolerance in rice.Plant physiology · 2022Article
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- Down-regulation of RalGTPase-Activating Protein Promotes Colitis-Associated Cancer via NLRP3 Inflammasome Activation.Cellular and molecular gastroenterology and hepatology · 2020Article
- Enhancement of Cutaneous Wound Healing by Dsg2 Augmentation of uPAR Secretion.The Journal of investigative dermatology · 2018Article
- Suppression of lung cancer progression by isoliquiritigenin through its metabolite 2, 4, 2', 4'-Tetrahydroxychalcone.Journal of experimental & clinical cancer research : CR · 2018Article
- Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes.International journal of molecular medicine · 2017Article
- The calcineurin-NFAT pathway allows for urokinase receptor-mediated beta3 integrin signaling to cause podocyte injury.Journal of molecular medicine (Berlin, Germany) · 2012Article
- The RalGEF-Ral Effector Signaling Network: The Road Less Traveled for Anti-Ras Drug Discovery.Genes & cancer · 2011Article
- Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38.The EMBO journal · 2002Article
- The Ral GTPase pathway in metastatic bladder cancer: key mediator and therapeutic target.Urologic oncologyReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The urokinase plasminogen activator receptor (uPAR) focuses extracellular protease activity to the cell surface, modulates cell adhesion and activates intracellular signal transduction pathways. In a range of cancers uPAR expression often has a negative correlation with prognosis. Here we show that uPAR transcription is stimulated by V12 H-Ras, the effector loop mutant V12 H-Ras G37 and constitutively-active RalA 72L. RalA-dependent transcription required the presence of the ATF2-like AP1-site at -70 bp and the c-Jun binding motif at -184 bp in the uPAR promoter. Consistent with this, both Gal4-c-Jun- and Gal4-ATF2-fusion proteins were activated by RalA signalling through phosphorylation of their activation domains at Ser63 and Ser73 of c-Jun or Thr69 and Thr71 of ATF2. A transdominant inhibitory mutant of c-Jun N-terminal kinase (JNK) failed to inhibit uPAR transcription demonstrating that JNK activation is not a prerequisite for RalA-dependent uPAR transcription. A dominant negative inhibitor of c-Src effectively inhibited RalA-dependent uPAR transcription identifying it as a downstream effector in the RalA signalling pathway. These data provide evidence for the existence of a novel signalling pathway that links RalA to the activation of uPAR transcription via a c-Src intermediate and activation of AP1.
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