ArticleOncogene2002
Repression of c-Cbl leads to enhanced G-CSF Jak-STAT signaling without increased cell proliferation.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 32 citations in OpenAlex.
- A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer.Frontiers in oncology · 2022Review
- Overexpression of E3 ubiquitin ligase Cbl attenuates endothelial dysfunction in diabetes mellitus by inhibiting the JAK2/STAT4 signaling and Runx3-mediated H3K4me3.Journal of translational medicine · 2021Article
- The Fibroblast Growth Factor Receptors in Breast Cancer: from Oncogenesis to Better Treatments.International journal of molecular sciences · 2020Review
- Article
- Article
- Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer.Cells · 2018Review
- Structural Determinants of the Gain-of-Function Phenotype of Human Leukemia-associated Mutant CBL Oncogene.The Journal of biological chemistry · 2017Article
- Mutations of c-Cbl in myeloid malignancies.Oncotarget · 2015Review
- CBL linker region and RING finger mutations lead to enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling via elevated levels of JAK2 and LYN.The Journal of biological chemistry · 2013Article
- Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases.Biochimica et biophysica acta · 2013Review
- PAK1-Nck regulates cyclin D1 promoter activity in response to prolactin.Molecular endocrinology (Baltimore, Md.) · 2011Article
- G-CSF stimulates Jak2-dependent Gab2 phosphorylation leading to Erk1/2 activation and cell proliferation.Cellular signalling · 2008Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Engagement of the Granulocyte-Colony-Stimulating Factor (G-CSF) receptor activates non-receptor protein tyrosine kinases Lyn and Jak2. We found that Lyn-deficient DT40 cells that express the G-CSF receptor (DT40GR) do not demonstrate G-CSF-induced mitogenic signaling. Lyn associates with and phosphorylates a small set of molecules, including c-Cbl. c-Cbl is an adaptor involved in cell growth and cytoskeletal reorganization, predominantly in hematopoietic cells. Using yeast two-hybrid analysis, we found that c-Cbl directly couples Lyn to PI 3-kinase. We also found that expression of the c-CblY731F mutant, which uncouples PI 3-kinase, resulted in the inhibition of G-CSF-induced proliferative signaling in DT40GR cells. As a complementary strategy, we sought to analyse the effects of c-Cbl deficiency in DT40GR cells. We isolated, cloned and sequenced the full-length cDNA for chicken c-Cbl and constructed antisense vectors. Antisense inhibition of c-Cbl expression in DT40GR cells led to enhanced Jak-STAT activation following G-CSF stimulation. Yet, this enhancement of Jak-STAT activation was associated with decreased G-CSF-induced PI 3-kinase activity and DNA synthesis. PI 3-kinase activity correlated with DNA synthesis and physiological levels of c-Cbl. Together, these data suggest that physiologic level of c-Cbl provides a growth stimulatory pathway for G-CSF and that enhanced Jak-STAT activation is not sufficient for G-CSF-induced growth.
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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.