Mast cell signaling: The role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants

Siraganian, Reuben P.; Castro, Rodrigo Orlandini de; Barbu, Emilia Alina; Zhang, Juan

doi:10.1016/j.febslet.2010.08.006

Cited by 137 publications

(131 citation statements)

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“…Spleen tyrosine kinase (Syk) has been identified as a central positive regulator of FcεRI-mediated signaling [11,12]. When activated by upstream signals and autophosphorylation, Syk phosphorylates other downstream molecules.…”

Section: Introductionmentioning

confidence: 99%

House Dust Mite-Specific Immunotherapy Alters the Basal Expression of T Regulatory and FcεRI Pathway Genes

Pevec

Marković

et al. 2012

Int Arch Allergy Immunol

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Background: Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Methods: Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG₄, nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Results: Decreased wheal sizes and VAS scores, negative challenges and increased sIgG₄ levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Conclusions: Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3.

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Section: Introductionmentioning

confidence: 99%

House Dust Mite-Specific Immunotherapy Alters the Basal Expression of T Regulatory and FcεRI Pathway Genes

Pevec

Marković

et al. 2012

Int Arch Allergy Immunol

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“…Syk phosphorylation is critical for propagating downstream signals (Costello et al, 1996;Zhang et al, 1996). Syk, in turn, stimulates phosphorylation of LAT, Gab2, Akt, PLCg, and Ca 2 þ influx (Siraganian et al, 2010;Yu et al, 2006). Activated Syk also directly or indirectly activities other downstream signaling molecules and MAP kinases, which promote the production of pro-inflammatory cytokines, including TNF-alpha and IL-4 (Rivera and Gilfillan, 2006).…”

Section: Discussionmentioning

confidence: 99%

The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA)

Zhang¹,

Park²,

Park³

2013

Journal of Ethnopharmacology

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“…Nevertheless, we propose that during fertilization Syk may be involved: 1) in the signal transduction pathway that mediates the actin cytoskeletal re-organization that finally leads to sperm engulfment. Evidences that support this hypothesis are those papers that propose Syk as a phagocytosis mediator (Greenberg et al, 1996;Crowley et al, 1997;Raeder et al, 1999;Berton et al, 2005;Tohyama and Yamamura, 2009) and also those reports that postulate the oocyte as a non-professional phagocyte (Bronson, 1998;Bronson 2009); and/or 2) in the signaling pathway that cause the transient increase in intracellular calcium that ultimately provoke the cortical granule exocytosis, like in mast cell and basophils, where Syk mediates the signaling that provoke degranulation (Siraganian et al, 2010;Ninomiya et al, 2010;Lu et al, 2012Lu et al, , 2014Matsuo et al, 2013).…”

Section: Fig5 Analysis Of Syk Tyrosine Phosphorylation State and Efmentioning

confidence: 95%

Activation of spleen tyrosine kinase (Syk) at fertilization in Rhinella arenarum eggs

Mouguelar¹,

Coux²

2014

Int. J. Dev. Biol.

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Recently, we have provided evidence for the involvement of a cytosolic tyrosine-phosphorylatable 70 kDa oocyte protein in Rhinella arenarum (Anura: Bufonidae) fertilization. The aim of the present work was to characterize its phosphorylation, determine the identity of this protein and establish its biological role during the fertilization process. Tyrosine phosphorylation of the 70 kDa protein was not observed in eggs activated with the calcium ionophore A23187. Pretreatment of oocytes with the tyrosine kinase inhibitor genistein effectively blocked the fertilization-dependent phosphorylation of the 70 kDa protein. In order to identify this protein, we examined the presence in amphibian oocytes of non-receptor 70 kDa tyrosine kinase members of the Syk/Zap70 and Tec families by RT-PCR using degenerate primers. We found that R. arenarum oocytes contain the transcripts coding for Syk and Tec kinases. Western blot analysis confirmed the presence of Syk protein in unfertilized oocytes and eggs. Studies using phospho-Syk specific antibodies showed that fertilization rapidly (less than 10 minutes) induces phosphorylation on Syk tyrosine residues (352 and 525/526) that are necessary for the activation of the enzyme. Finally, specific inhibition of Syk with the R406 compound provoked a diminished fertilization score, thereby confirming a functional role of the Syk protein during R. arenarum fertilization. To our knowledge this is the first time that Syk is described as a player in the signaling cascade activated after fertilization.

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Mast cell signaling: The role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants

Cited by 137 publications

References 50 publications

House Dust Mite-Specific Immunotherapy Alters the Basal Expression of T Regulatory and FcεRI Pathway Genes

House Dust Mite-Specific Immunotherapy Alters the Basal Expression of T Regulatory and FcεRI Pathway Genes

The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA)

Activation of spleen tyrosine kinase (Syk) at fertilization in Rhinella arenarum eggs

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