肥大细胞信号转导：蛋白酪氨酸激酶 Syk 的作用、激活及其新途径参与者的筛选方法。
Mast cell signaling: the role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants.
机构信息
Receptors and Signal Transduction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
FEBS Lett. 2010 Dec 15;584(24):4933-40. doi: 10.1016/j.febslet.2010.08.006. Epub 2010 Aug 7.
Abstract
The aggregation by antigen of the IgE bound to its high affinity receptor on mast cells initiates a complex series of biochemical events that result in the release of inflammatory mediators. The essential role of the protein tyrosine kinase Syk has been appreciated for some time, and newer results have defined the mechanism of its activation. The use of siRNA has defined the relative contribution of Syk, Fyn and Gab2 to signaling and has made possible a screening study to identify previously unrecognized molecules that are involved in these pathways.
摘要
抗原与肥大细胞表面高亲和力受体结合的 IgE 聚集，引发了一系列复杂的生化事件，导致炎症介质的释放。蛋白酪氨酸激酶 Syk 的重要作用已经被人们认识了一段时间，而新的研究结果定义了其激活的机制。siRNA 的使用定义了 Syk、Fyn 和 Gab2 在信号转导中的相对贡献，并使得进行筛选研究以鉴定以前未被识别的参与这些途径的分子成为可能。
相似文献
1
Mast cell signaling: the role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants.肥大细胞信号转导：蛋白酪氨酸激酶 Syk 的作用、激活及其新途径参与者的筛选方法。
FEBS Lett. 2010 Dec 15;584(24):4933-40. doi: 10.1016/j.febslet.2010.08.006. Epub 2010 Aug 7.
2
The limited contribution of Fyn and Gab2 to the high affinity IgE receptor signaling in mast cells.Fyn 和 Gab2 对肥大细胞高亲和力 IgE 受体信号转导的有限贡献。
J Biol Chem. 2010 May 21;285(21):15761-8. doi: 10.1074/jbc.M110.109413. Epub 2010 Mar 24.
3
The Src family kinase Fgr is critical for activation of mast cells and IgE-mediated anaphylaxis in mice.Src 家族激酶 Fgr 对于小鼠肥大细胞的激活和 IgE 介导的过敏反应至关重要。
J Immunol. 2011 Aug 15;187(4):1807-15. doi: 10.4049/jimmunol.1100296. Epub 2011 Jul 11.
4
Once phosphorylated, tyrosines in carboxyl terminus of protein-tyrosine kinase Syk interact with signaling proteins, including TULA-2, a negative regulator of mast cell degranulation.一旦磷酸化，蛋白酪氨酸激酶 Syk 的羧基末端的酪氨酸与信号蛋白相互作用，包括 TULA-2，一种肥大细胞脱粒的负调节剂。
J Biol Chem. 2012 Mar 9;287(11):8194-204. doi: 10.1074/jbc.M111.326850. Epub 2012 Jan 20.
5
Regulation of microtubule formation in activated mast cells by complexes of gamma-tubulin with Fyn and Syk kinases.γ-微管蛋白与Fyn和Syk激酶复合物对活化肥大细胞中微管形成的调控
J Immunol. 2006 Jun 15;176(12):7243-53. doi: 10.4049/jimmunol.176.12.7243.
6
The adaptor molecule CIN85 regulates Syk tyrosine kinase level by activating the ubiquitin-proteasome degradation pathway.衔接分子CIN85通过激活泛素-蛋白酶体降解途径来调节Syk酪氨酸激酶水平。
J Immunol. 2007 Aug 15;179(4):2089-96. doi: 10.4049/jimmunol.179.4.2089.
7
Sustained activation of the tyrosine kinase Syk by antigen in mast cells requires local Ca2+ influx through Ca2+ release-activated Ca2+ channels.肥大细胞中抗原持续激活酪氨酸激酶Syk需要通过钙释放激活钙通道使局部钙离子内流。
J Biol Chem. 2008 Nov 14;283(46):31348-55. doi: 10.1074/jbc.M804942200. Epub 2008 Sep 19.
8
Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells.Dectin-1 介导的信号转导通过大鼠肥大细胞中的脾酪氨酸激酶 (Syk) 导致特征性基因表达和细胞因子分泌。
J Biol Chem. 2014 Nov 7;289(45):31565-75. doi: 10.1074/jbc.M114.581322. Epub 2014 Sep 22.
9
The protein tyrosine kinase syk activity is reduced by clustering the mast cell function-associated antigen.通过使肥大细胞功能相关抗原聚集，可降低蛋白酪氨酸激酶syk的活性。
Eur J Immunol. 2001 May;31(5):1571-81. doi: 10.1002/1521-4141(200105)31:5<1571::AID-IMMU1571>3.0.CO;2-U.
10
Gi-mediated activation of the Syk kinase by the receptor mimetic basic secretagogues of mast cells: role in mediating arachidonic acid/metabolites release.
J Immunol. 2001 Jul 1;167(1):475-81. doi: 10.4049/jimmunol.167.1.475.
引用本文的文献
1
Beyond Antihistamines: How Biologic and Small-Molecule Therapies Are Transforming Chronic Spontaneous Urticaria Care in Adults.超越抗组胺药：生物制剂和小分子疗法如何改变成人慢性自发性荨麻疹的治疗
Clin Drug Investig. 2025 Sep 17. doi: 10.1007/s40261-025-01480-5.
2
Unique compound with anti-allergic action: inhibition of Lyn kinase activity by KIRA6.具有抗过敏作用的独特化合物：KIRA6对Lyn激酶活性的抑制作用。
Front Pharmacol. 2025 Jul 25;16:1625798. doi: 10.3389/fphar.2025.1625798. eCollection 2025.
3
Aberrant Activation of Mast Cells: Molecular Mechanisms and Targets for Intervention.肥大细胞的异常激活：分子机制与干预靶点
Clin Rev Allergy Immunol. 2025 Jun 20;68(1):60. doi: 10.1007/s12016-025-09065-y.
4
Transcriptomic signatures of atheroresistance in the human atrium and ventricle highlight potential candidates for targeted atherosclerosis therapeutics.人类心房和心室中抗动脉粥样硬化的转录组特征突出了靶向动脉粥样硬化治疗的潜在候选物。
Biochem Biophys Rep. 2025 Apr 8;42:102007. doi: 10.1016/j.bbrep.2025.102007. eCollection 2025 Jun.
5
Anti-microbial cetylpyridinium chloride suppresses mast cell function by targeting tyrosine phosphorylation of Syk kinase.抗菌性氯化十六烷基吡啶通过靶向脾酪氨酸激酶的酪氨酸磷酸化来抑制肥大细胞功能。
J Immunotoxicol. 2024 Dec;21(1):2443397. doi: 10.1080/1547691X.2024.2443397. Epub 2025 Jan 15.
6
Synovial mast cells and osteoarthritis: Current understandings and future perspectives.滑膜肥大细胞与骨关节炎：当前认识与未来展望
Heliyon. 2024 Dec 6;10(24):e41003. doi: 10.1016/j.heliyon.2024.e41003. eCollection 2024 Dec 30.
7
Simultaneous multicolor fluorescence imaging using PSF splitting.基于 PSF 分裂的同时多色荧光成像。
Nat Methods. 2024 Oct;21(10):1801-1805. doi: 10.1038/s41592-024-02383-7. Epub 2024 Sep 6.
8
Syk protein inhibitors treatment for the allergic symptoms associated with hyper immunoglobulin E syndromes: A focused on a computational approach.Syk 蛋白抑制剂治疗与高免疫球蛋白 E 综合征相关的过敏症状：基于计算方法的研究。
Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241282030. doi: 10.1177/03946320241282030.
9
Effect of Isoscopoletin on Cytokine Expression in HaCaT Keratinocytes and RBL-2H3 Basophils: Preliminary Study.异土木香内酯对 HaCaT 角质形成细胞和 RBL-2H3 嗜碱性粒细胞细胞因子表达的影响：初步研究。
Int J Mol Sci. 2024 Jun 24;25(13):6908. doi: 10.3390/ijms25136908.
10
Allergen-specific IgA and IgG antibodies as inhibitors of mast cell function in food allergy.作为食物过敏中肥大细胞功能抑制剂的变应原特异性 IgA 和 IgG 抗体。
Front Allergy. 2024 Jun 11;5:1389669. doi: 10.3389/falgy.2024.1389669. eCollection 2024.
本文引用的文献
1
Tyrosines in the carboxyl terminus regulate Syk kinase activity and function.羧基末端的酪氨酸调节 Syk 激酶的活性和功能。
J Biol Chem. 2010 Aug 20;285(34):26674-84. doi: 10.1074/jbc.M110.134262. Epub 2010 Jun 16.
2
Small interfering RNA screen for phosphatases involved in IgE-mediated mast cell degranulation.小干扰 RNA 筛选 IgE 介导的肥大细胞脱颗粒涉及的磷酸酶。
J Immunol. 2010 Jun 15;184(12):7178-85. doi: 10.4049/jimmunol.0904169. Epub 2010 May 7.
3
The SYK tyrosine kinase: a crucial player in diverse biological functions.SYK 酪氨酸激酶：多种生物学功能的关键参与者。
Nat Rev Immunol. 2010 Jun;10(6):387-402. doi: 10.1038/nri2765.
4
The limited contribution of Fyn and Gab2 to the high affinity IgE receptor signaling in mast cells.Fyn 和 Gab2 对肥大细胞高亲和力 IgE 受体信号转导的有限贡献。
J Biol Chem. 2010 May 21;285(21):15761-8. doi: 10.1074/jbc.M110.109413. Epub 2010 Mar 24.
5
Molecular basis of calcium signaling in lymphocytes: STIM and ORAI.淋巴细胞钙离子信号转导的分子基础：STIM 和 ORAI。
Annu Rev Immunol. 2010;28:491-533. doi: 10.1146/annurev.immunol.021908.132550.
6
Adapters in the organization of mast cell signaling.衔接子在肥大细胞信号转导中的作用。
Immunol Rev. 2009 Nov;232(1):195-217. doi: 10.1111/j.1600-065X.2009.00834.x.
7
Cooperation of adapter molecules in proximal signaling cascades during allergic inflammation.过敏炎症中近端信号级联反应中衔接分子的协作。
Immunol Rev. 2009 Nov;232(1):99-114. doi: 10.1111/j.1600-065X.2009.00825.x.
8
Mechanisms of mast cell signaling in anaphylaxis.过敏反应中肥大细胞信号传导的机制。
J Allergy Clin Immunol. 2009 Oct;124(4):639-46; quiz 647-8. doi: 10.1016/j.jaci.2009.08.035.
9
FcepsilonRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation.低抗原浓度诱导的FcepsilonRI激活在无脱颗粒的情况下导致核信号。
Mol Immunol. 2009 Aug;46(13):2539-47. doi: 10.1016/j.molimm.2009.05.013. Epub 2009 Jun 21.
10
Calcium signaling in immune cells.免疫细胞中的钙信号传导。
Nat Immunol. 2009 Jan;10(1):21-7. doi: 10.1038/ni.f.220.
Zotero 插件