ArticleScience signaling2013
Dysregulated RasGRP1 responds to cytokine receptor input in T cell leukemogenesis.
Article in Science signaling, 2013. 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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Who cites it
36 citing papers in PubMed, 2 citations in OpenAlex.
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Phosphorylation of RasGRP1 by Shc3 prevents RasGRP1 degradation and contributes to Ras/c-Jun activation in hepatocellular carcinoma.Molecular and cellular biochemistry · 2024Article
- Article
- Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.Cell cycle (Georgetown, Tex.) · 2024Review
- Systematic Analysis to Identify the MIR99AHG-has-miR-21-5p-Journal of Cancer · 2024Article
- Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress.Blood · 2023Article
- S1P-S1PR3-RAS promotes the progression of S1PR3Leukemia · 2023Article
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients.Biomolecules · 2022Article
- Investigating increased hematopoietic stem cell fitness in a novel mouse model.Small GTPases · 2022Article
- Article
- Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.European journal of immunology · 2021Article
- Regulation of the Small GTPase Ras and Its Relevance to Human Disease.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Interleukin (IL)-7 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- RasGRP1 is a causal factor in the development of l-DOPA-induced dyskinesia in Parkinson's disease.Science advances · 2020Article
- mTOR and other effector kinase signals that impact T cell function and activity.Immunological reviews · 2019Review
- High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.Cell reports · 2019Article
- Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.International journal of molecular sciences · 2018Review
- Article
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18 authors at 2 institutions in 1 country.
Funding
Abstract
Enhanced signaling by the small guanosine triphosphatase Ras is common in T cell acute lymphoblastic leukemia/lymphoma (T-ALL), but the underlying mechanisms are unclear. We identified the guanine nucleotide exchange factor RasGRP1 (Rasgrp1 in mice) as a Ras activator that contributes to leukemogenesis. We found increased RasGRP1 expression in many pediatric T-ALL patients, which is not observed in rare early T cell precursor T-ALL patients with KRAS and NRAS mutations, such as K-Ras(G12D). Leukemia screens in wild-type mice, but not in mice expressing the mutant K-Ras(G12D) that encodes a constitutively active Ras, yielded frequent retroviral insertions that led to increased Rasgrp1 expression. Rasgrp1 and oncogenic K-Ras(G12D) promoted T-ALL through distinct mechanisms. In K-Ras(G12D) T-ALLs, enhanced Ras activation had to be uncoupled from cell cycle arrest to promote cell proliferation. In mouse T-ALL cells with increased Rasgrp1 expression, we found that Rasgrp1 contributed to a previously uncharacterized cytokine receptor-activated Ras pathway that stimulated the proliferation of T-ALL cells in vivo, which was accompanied by dynamic patterns of activation of effector kinases downstream of Ras in individual T-ALLs. Reduction of Rasgrp1 abundance reduced cytokine-stimulated Ras signaling and decreased the proliferation of T-ALL in vivo. The position of RasGRP1 downstream of cytokine receptors as well as the different clinical outcomes that we observed as a function of RasGRP1 abundance make RasGRP1 an attractive future stratification marker for T-ALL.
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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.