ArticleOncogene2003
c-Cbl is a critical modulator of the Ron tyrosine kinase receptor.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 55 citations in OpenAlex.
- MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity.Frontiers in immunology · 2020Review
- Peritumoral Cbl is a strong independent prognostic marker after curative resection of hepatocellular carcinoma.Oncotarget · 2015Article
- Redox biology in normal cells and cancer: restoring function of the redox/Fyn/c-Cbl pathway in cancer cells offers new approaches to cancer treatment.Free radical biology & medicine · 2015Review
- Article
- Autoinhibition of the Ron receptor tyrosine kinase by the juxtamembrane domain.Cell communication and signaling : CCS · 2014Article
- Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling.Cold Spring Harbor perspectives in biology · 2013Review
- Pathogenesis of RON receptor tyrosine kinase in cancer cells: activation mechanism, functional crosstalk, and signaling addiction.Journal of biomedical research · 2013Review
- MSP-RON signalling in cancer: pathogenesis and therapeutic potential.Nature reviews. Cancer · 2013Review
- Endocytosis of receptor tyrosine kinases.Cold Spring Harbor perspectives in biology · 2013Review
- Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases.Biochimica et biophysica acta · 2013Review
- Short-Form Ron Promotes Spontaneous Breast Cancer Metastasis through Interaction with Phosphoinositide 3-Kinase.Genes & cancer · 2011Article
- RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma.Cancer biology & therapy · 2011Article
- Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase.Molecular cancer · 2010Article
- Degradation of activated protein kinases by ubiquitination.Annual review of biochemistry · 2009Review
- Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160.Journal of experimental & clinical cancer research : CR · 2008Article
- HIV-1 Tat mediates degradation of RON receptor tyrosine kinase, a regulator of inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates.The EMBO journal · 2008Article
- c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses.The Biochemical journal · 2005Review
- The carboxyl terminus of VEGFR-2 is required for PKC-mediated down-regulation.Molecular biology of the cell · 2005Article
- Development of an LC-MALDI method for the analysis of protein complexes.Journal of the American Society for Mass Spectrometry · 2004Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein (MSP), activates multiple signaling pathways by recruiting several positive regulators to a multifunctional docking site. Here we show that stimulation by MSP also recruits a negative regulator, the c-Cbl ubiquitin ligase, to the multifunctional docking site as well as to a juxtamembrane tyrosine autophosphorylation site. c-Cbl recruitment to these two sites results in polyubiquitylation of Ron molecules, which are subsequently sorted for endocytosis and degradation. Both the phosphotyrosine binding domain of c-Cbl and its RING domain are essential for downregulation of Ron. Although Ron and c-Cbl are found also in physical complexes that include Grb2, these associations are insufficient for productive ubiquitylation of Ron. Our results shed light on the mechanism of receptor desensitization mediated by c-Cbl and its binding partner Grb2.
Indexed as
Identifiers
What OpenQuestion holds
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.