ArticleThe Journal of experimental medicine1997
Distinct Ras effector pathways are involved in Fc epsilon R1 regulation of the transcriptional activity of Elk-1 and NFAT in mast cells.
Article in The Journal of experimental medicine, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 71 citations in OpenAlex.
- CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells.International journal of molecular sciences · 2023Article
- Review
- Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.Frontiers in cell and developmental biology · 2021Article
- SLAP Is a Negative Regulator of FcεRI Receptor-Mediated Signaling and Allergic Response.Frontiers in immunology · 2019Article
- Emodin Isolated from Polygoni cuspidati Radix Inhibits TNF-α and IL-6 Release by Blockading NF-κB and MAP Kinase Pathways in Mast Cells Stimulated with PMA Plus A23187.Biomolecules & therapeutics · 2013Article
- p15(INK4b) plays a crucial role in murine lymphoid development and tumorigenesis.Carcinogenesis · 2012Article
- Phospholipase Cγ2 (PLCγ2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses.The Journal of biological chemistry · 2011Article
- Receptor signaling in immune cell development and function.Immunologic research · 2011Article
- Regulation of mast cell responses in health and disease.Critical reviews in immunology · 2011Review
- Expression, localisation and functional activation of NFAT-2 in normal human skin, psoriasis, and cultured keratocytes.International journal of clinical and experimental medicine · 2009Article
- SWAP-70 regulates mast cell FcepsilonRI-mediated signaling and anaphylaxis.European journal of immunology · 2008Article
- Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells.The Journal of experimental medicine · 2006Article
- Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus.Molecular and cellular biology · 2004Article
- Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in lymphocytes.The Journal of experimental medicine · 2000Article
- Spatial and temporal regulation of protein kinase D (PKD).The EMBO journal · 2000Article
- Review
- Small GTPases in lymphocyte biology: Rho proteins take center stage.Immunologic research · 1999Review
- Rac-1 regulates nuclear factor of activated T cells (NFAT) C1 nuclear translocation in response to Fcepsilon receptor type 1 stimulation of mast cells.The Journal of experimental medicine · 1998Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of Ras GTPases is a conserved feature of antigen receptor signaling, including Fc epsilon R1 activation of mast cells. Antigenic cross-linking of the Fc epsilon R1 on mast cells results in secretion of allergic mediators and induction of immediate early and cytokine genes. Here we examine the role of Ras in coupling the Fc epsilon R1 to transcriptional regulation. The transcription factors Elk-1, an immediate early gene regulator and the nuclear factor of activated T cells (NFAT), in the context of the IL-4 gene, are identified as Ras targets in mast cells. Ras mediates diverse effects via its diverse effector pathways, which may include other members of the Ras GTPase family such as RhoA and Rac-1. We observe that Elk-1 and NFAT are targeted by distinct Ras effector pathways in mast cells. Activation of the "classical" Ras/Raf-1/MEK/ ERK cascade is necessary and sufficient for Fc epsilon R1 induction of Elk-1. Ras function is required, but not sufficient for Fc epsilon R1 induction of NFAT. However, activation or inhibition of Ras markedly shifts the antigen dose-response for Fc epsilon R1 induction of NFAT. The effector pathway for Ras activation of NFAT is not Raf-1/MEK. We identify that the Rac-1 GTPase is critical in Fc epsilon R1 regulation of NFAT, acting either in parallel with or as an effector of Ras. These data place Ras in a crucial position in mast cells, regulating disparate nuclear targets. Moreover, we identify that two GTPases, Ras and Rac-1, are important regulators of NFAT, and therefore of cytokine expression in mast cells.
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