ArticleThe EMBO journal1999
Activation of the Raf/MAP kinase cascade by the Ras-related protein TC21 is required for the TC21-mediated transformation of NIH 3T3 cells.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
36 citing papers in PubMed, 83 citations in OpenAlex.
- Active R-RAS2/TC21 prevents cell cycle arrest and morphological alterations in mouse embryonic fibroblasts lacking RAS proteins.Oncogene · 2025Article
- A mode of action protein based approach that characterizes the relationships among most major diseases.Scientific reports · 2025Article
- Transfection of Sponge Cells and Intracellular Localization of Cancer-Related MYC, RRAS2, and DRG1 Proteins.Marine drugs · 2023Article
- Article
- R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells.Cell communication and signaling : CCS · 2021Article
- TC21/RRas2 regulates glycoprotein VI-FcRγ-mediated platelet activation and thrombus stability.Journal of thrombosis and haemostasis : JTH · 2018Article
- R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Article
- Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.Nature biotechnology · 2016Article
- Two clinical phenotypes in polycythemia vera.The New England journal of medicine · 2014Article
- Article
- siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin.World journal of gastroenterology · 2012Article
- The Ras-like protein R-Ras2/TC21 is important for proper mammary gland development.Molecular biology of the cell · 2012Article
- Structural and spatial determinants regulating TC21 activation by RasGRF family nucleotide exchange factors.Molecular biology of the cell · 2009Article
- Essential function for the GTPase TC21 in homeostatic antigen receptor signaling.Nature immunology · 2009Article
- The p38 MAPK stress pathway as a tumor suppressor or more?Frontiers in bioscience : a journal and virtual library · 2008Review
- The neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42.The Journal of cell biology · 2007Article
- H-Ras, R-Ras, and TC21 differentially regulate ureteric bud cell branching morphogenesis.Molecular biology of the cell · 2006Article
- Oncogenic Ras-mediated downregulation of Gadd153/CHOP is required for Ras-induced cellular transformation.Oncogene · 2005Article
- Human RAS superfamily proteins and related GTPases.Science's STKE : signal transduction knowledge environment · 2004Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
TC21 is a member of the Ras superfamily of small GTP-binding proteins and, like Ras, has been implicated in the regulation of growth-stimulating pathways. Point mutations introduced into TC21 based on equivalent H-Ras oncogenic mutations are transforming in cultured cells, and oncogenic mutations in TC21 have been isolated from several human tumours. The mechanism of TC21 signalling in transformation is poorly understood. While activation of the serine/threonine kinases Raf-1 and B-Raf has been implicated in signalling pathways leading to transformation by H-Ras, it has been argued that TC21 does not activate Raf-1 or B-Raf. Since the Raf-signalling pathway is important in transformation by other Ras proteins, we assessed whether the Raf pathway is important to transformation by TC21. Raf-1 and B-Raf are constitutively active in TC21-transformed cells and the ERK/MAPK cascade is required for the maintenance of the transformed state. We demonstrate that oncogenic V23 TC21, like Ras, interacts with Raf-1 and B-Raf (but not with A-Raf), resulting in the translocation of the Raf proteins to the plasma membrane and in their activation. Furthermore, using point mutations in the effector loop of TC21, we show that the interaction of TC21 with Raf-1 is crucial for transformation.
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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.