ArticleProceedings of the National Academy of Sciences of the United States of America2004
Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 81 citations in OpenAlex.
- Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFα inhibitors.Arthritis research & therapy · 2015Trial
- Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma.Cancer research · 2023Article
- Integrin β1 regulates marginal zone B cell differentiation and PI3K signaling.The Journal of experimental medicine · 2023Article
- Review
- Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis.Frontiers in immunology · 2022Article
- Article
- The critical role of RasGRP4 in the growth of diffuse large B cell lymphoma.Cell communication and signaling : CCS · 2019Article
- Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells.Scientific reports · 2018Article
- Article
- GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma.Cell reports · 2018Article
- Importance of the REM (Ras exchange) domain for membrane interactions by RasGRP3.Biochimica et biophysica acta. Biomembranes · 2017Article
- A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.eLife · 2017Article
- RasGRP3 Mediates MAPK Pathway Activation in GNAQ Mutant Uveal Melanoma.Cancer cell · 2017Article
- Article
- Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer.Molecular cancer research : MCR · 2015Article
- RasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase.Nature communications · 2014Article
- Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP.Bioorganic & medicinal chemistry · 2014Article
- Function of RasGRP3 in the formation and progression of human breast cancer.Molecular cancer · 2014Article
- RasGRP Ras guanine nucleotide exchange factors in cancer.Frontiers in biology · 2013Article
- Regulation of ras exchange factors and cellular localization of ras activation by lipid messengers in T cells.Frontiers in immunology · 2013Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ras signaling pathway plays a critical role in B lymphocyte development and activation, but its activation mechanism has not been well understood. At least one mode of Ras regulation in B cells involves a Ras-guanyl nucleotide exchange factor, RasGRP3. We demonstrate here that RasGRP3 undergoes phosphorylation at Thr-133 upon B cell receptor cross-linking, thereby resulting in its activation. Deletion of phospholipase C-gamma2 or pharmacological interference with conventional PKCs resulted in marked reduction in both Thr-133 phosphorylation and Ras activation. Moreover, mutation of Thr-133 in RasGRP3 alone severely impaired its ability to activate Ras in B cell receptor signaling. Hence, our data suggest that PKC, after being activated by diacylglycerol, phosphorylates RasGRP3, thereby contributing to its full activation.
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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.