What precedes the initial tyrosine phosphorylation of the high affinity IgE receptor in antigen‐activated mast cell?

Bugajev, Viktor; Bambousková, Monika; Dráber, Petr

doi:10.1016/j.febslet.2010.08.045

Cited by 28 publications

(27 citation statements)

References 40 publications

(67 reference statements)

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“…In nonactivated WT cells both adaptor proteins, NTAL and LAT, as well as FcεRI β and γ subunits are only weakly tyrosine phosphorylated, because of the equilibrium between kinases and phosphatases and/or decreased access of the kinase to their substrates [46]. Quiescent cells also exhibit low [Ca 2+ ] i and standard gene expression (Transcription profile 1; Figure 9A).…”

Section: Discussionmentioning

confidence: 99%

Multiple Regulatory Roles of the Mouse Transmembrane Adaptor Protein NTAL in Gene Transcription and Mast Cell Physiology

et al. 2014

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Non-T cell activation linker (NTAL; also called LAB or LAT2) is a transmembrane adaptor protein that is expressed in a subset of hematopoietic cells, including mast cells. There are conflicting reports on the role of NTAL in the high affinity immunoglobulin E receptor (FcεRI) signaling. Studies carried out on mast cells derived from mice with NTAL knock out (KO) and wild type mice suggested that NTAL is a negative regulator of FcεRI signaling, while experiments with RNAi-mediated NTAL knockdown (KD) in human mast cells and rat basophilic leukemia cells suggested its positive regulatory role. To determine whether different methodologies of NTAL ablation (KO vs KD) have different physiological consequences, we compared under well defined conditions FcεRI-mediated signaling events in mouse bone marrow-derived mast cells (BMMCs) with NTAL KO or KD. BMMCs with both NTAL KO and KD exhibited enhanced degranulation, calcium mobilization, chemotaxis, tyrosine phosphorylation of LAT and ERK, and depolymerization of filamentous actin. These data provide clear evidence that NTAL is a negative regulator of FcεRI activation events in murine BMMCs, independently of possible compensatory developmental alterations. To gain further insight into the role of NTAL in mast cells, we examined the transcriptome profiles of resting and antigen-activated NTAL KO, NTAL KD, and corresponding control BMMCs. Through this analysis we identified several genes that were differentially regulated in nonactivated and antigen-activated NTAL-deficient cells, when compared to the corresponding control cells. Some of the genes seem to be involved in regulation of cholesterol-dependent events in antigen-mediated chemotaxis. The combined data indicate multiple regulatory roles of NTAL in gene expression and mast cell physiology.

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Section: Discussionmentioning

confidence: 99%

Multiple Regulatory Roles of the Mouse Transmembrane Adaptor Protein NTAL in Gene Transcription and Mast Cell Physiology

et al. 2014

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“…The exact molecular mechanism behind this event is not completely understood, but it is expected that there are changes in access of LYN to tyrosine residues in the ITAM motifs of β and γ chains and/or decrease dephosphorylation of the target phosphotyrosines (Bugajev et al, 2010). Phosphorylation of FcεRI β and γ chains facilitates recruitment of LYN and SYK, respectively, and their activation.…”

Section: Signal Transductionmentioning

confidence: 99%

Signal transduction and chemotaxis in mast cells

Dráber

Hálová

Polakovičová

et al. 2016

European Journal of Pharmacology

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Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis.

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“…Studies have shown that the infiltration and release of mast cell (MC) in colon are the cause of the symptom in IBS patients, and are closely related to visceral hypersensitivity in patients with IBS (Ohman & Simren, 2010). During the MC activation, cytokines IL-4 and -9 secreted by T cells play an important role (Bugajev et al, 2010; Kashiwada et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

PDIA3 gene induces visceral hypersensitivity in rats with irritable bowel syndrome through the dendritic cell-mediated activation of T cells

Zhuang

Zhang

Wang

et al. 2016

PeerJ

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This study investigated the mechanism of protein disulfide-isomerase A3 (PDIA3)-induced visceral hypersensitivity in irritable bowel syndrome (IBS). Rats were treated with saline (control), acetic acid and restraint stress (IBS model), empty vector (RNAi control) and PDIA3-RNAi vector (PDIA3-RNAi). Mesenteric lymph node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated for co-cultivation. Compared with control, MLNDCs co-cultured with CD4+ or CD8+ T cells showed an increased ability to promote T cell proliferation and produced more IL-4 or IL-9 secretion. Compared with the RNAi control, MLNDCs from the PDIA3 knockdown models were less effective in promoting the proliferation of CD4+/CD8+ T cells. It is concluded that PDIA3 plays an important role in the development of IBS through the DC-mediated activation of T cells, resulting in degranulation of MCs and visceral hypersensitivity.

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What precedes the initial tyrosine phosphorylation of the high affinity IgE receptor in antigen‐activated mast cell?

Cited by 28 publications

References 40 publications

Multiple Regulatory Roles of the Mouse Transmembrane Adaptor Protein NTAL in Gene Transcription and Mast Cell Physiology

Multiple Regulatory Roles of the Mouse Transmembrane Adaptor Protein NTAL in Gene Transcription and Mast Cell Physiology

Signal transduction and chemotaxis in mast cells

PDIA3 gene induces visceral hypersensitivity in rats with irritable bowel syndrome through the dendritic cell-mediated activation of T cells

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