ArticleThe Journal of cell biology2000
Cdc42 and Rac stimulate exocytosis of secretory granules by activating the IP(3)/calcium pathway in RBL-2H3 mast cells.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 145 citations in OpenAlex.
- Article
- Review
- RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis.Journal of leukocyte biology · 2024Article
- Article
- Pharmacologic targeting of Cdc42 GTPase by a small molecule Cdc42 activity-specific inhibitor prevents platelet activation and thrombosis.Scientific reports · 2021Article
- MYO1F Regulates IgE and MRGPRX2-Dependent Mast Cell Exocytosis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Pleiotropic Roles of Calmodulin in the Regulation of KRas and Rac1 GTPases: Functional Diversity in Health and Disease.International journal of molecular sciences · 2020Review
- The RhoGAP SPV-1 regulates calcium signaling to control the contractility of the Caenorhabditis elegans spermatheca during embryo transits.Molecular biology of the cell · 2019Article
- SAD-A Promotes Glucose-Stimulated Insulin Secretion Through Phosphorylation and Inhibition of GDIα in Male Islet β Cells.Endocrinology · 2018Article
- Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.The Journal of clinical investigation · 2016Article
- Rac1-dependent phosphorylation and focal adhesion recruitment of myosin IIA regulates migration and mechanosensing.Current biology : CB · 2015Article
- Activation of Cdc42 is necessary for sustained oscillations of Ca2+ and PIP2 stimulated by antigen in RBL mast cells.Biology open · 2014Article
- WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells.Molecular cancer · 2014Article
- Granule protein processing and regulated secretion in neutrophils.Frontiers in immunology · 2014Review
- Mast cell mediators: their differential release and the secretory pathways involved.Frontiers in immunology · 2014Review
- Rho GTPases, phosphoinositides, and actin: a tripartite framework for efficient vesicular trafficking.Small GTPases · 2014Review
- Secrets of platelet exocytosis - what do we really know about platelet secretion mechanisms?British journal of haematology · 2013Article
- Rho GTPases in platelet function.Journal of thrombosis and haemostasis : JTH · 2013Review
- Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic β-Cells.The Journal of biological chemistry · 2012Article
- P2Y2 receptor-mediated lymphotoxin-α secretion regulates intercellular cell adhesion molecule-1 expression in vascular smooth muscle cells.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We have expressed dominant-active and dominant-negative forms of the Rho GTPases, Cdc42 and Rac, using vaccinia virus to evaluate the effects of these mutants on the signaling pathway leading to the degranulation of secretory granules in RBL-2H3 cells. Dominant-active Cdc42 and Rac enhance antigen-stimulated secretion by about twofold, whereas the dominant-negative mutants significantly inhibit secretion. Interestingly, treatment with the calcium ionophore, A23187, and the PKC activator, PMA, rescues the inhibited levels of secretion in cells expressing the dominant-negative mutants, implying that Cdc42 and Rac act upstream of the calcium influx pathway. Furthermore, cells expressing the dominant-active mutants exhibit elevated levels of antigen-stimulated IP(3) production, an amplified antigen-stimulated calcium response consisting of both calcium release from internal stores and influx from the extracellular medium, and an increase in aggregate formation of the IP(3) receptor. In contrast, cells expressing the dominant-negative mutants display the opposite phenotypes. Finally, we are able to detect an in vitro interaction between Cdc42 and PLCgamma1, the enzyme immediately upstream of IP(3) formation. Taken together, these findings implicate Cdc42 and Rac in regulating the exocytosis of secretory granules by stimulation of IP(3) formation and calcium mobilization upon antigen stimulation.
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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.