Asc(Tyr-144), 磷酸化特异性抗体, AP5631

背景描述:宿主和病原体相关的细胞质双链DNA触发了独立于NALP3的炎症小体的激活,该炎症小体激活了caspase-1,导致促白介素1β的成熟和炎症。几项研究已分离出AIM2(黑色素瘤2中不存在)作为候选的胞质DNA感应蛋白,其中包含N端吡啶结构域和C端寡核苷酸结合结构域。干扰素-β诱导的转录本的筛选确定了AIM2基因表达。AIM2蛋白结合双链DNA,募集了炎性体衔接子ASC,并定位于包含斑点的ASC。AIM2和ASC形成一个焦磷酸核小体,它诱导由caspase-1介导的焦细胞凋亡。Asc可以Syk和JNK依赖性方式在Tyr-144磷酸化。

Host- and pathogen-associated cytoplasmic double-stranded DNA triggers the activation of a NALP3-independent inflammasome, which activates caspase-1, leading to maturation of pro-interleukin-1beta and inflammation. Several studies have isolated AIM2 (absent in melanoma 2) as a candidate cytoplasmic-DNA-sensing protein that contains an N-terminal pyrin domain and C-terminal oligonucleotide binding domain. A screen for transcripts induced by interferon-beta identified AIM2 gene expression. AIM2 protein bound double-stranded DNA, recruited the inflammasome adaptor ASC, and localized to ASC containing speckles. AIM2 and ASC form a pyroptosome, which induces pyroptotic cell death mediated by caspase-1. Asc can be phosphorylated at Tyr-144 in a Syk and JNK-dependent manner. This phosphorylation is critical for Asc speck formation and Caspase-1 activation.

参考资料:

Hara, H. et al. (2013) Nature Immunol. 14(12):1247. 
Roberts, T.L. et al. (2009). Science. 323(5917):1057.
Bürckstümmer, T. et al. (2009). Nat Immunol. 10(3):266.

实验图片参考:

Western blot analysis of mouse macrophage J774A.1 cells stimulated with pervanadate (1 mM for 30 min.), then untreated (-) or treated (+) with alkaline phosphatase. The blot was probed with rabbit polyclonal anti-Asc (Tyr-144) phospho-specific antibody (AP5631) at 1:500.
Immunocytochemical labeling of Asc (Tyr-144) in inflammasomes. Paraformaldehyde fixed J774 cells were primed with LPS and treated with nigericin. Cells were co-labeled with DAPI, a caspase-1 inhibitor (FAM-YVAD-FMK), and anti-Asc (Tyr-144) phosphospecific antibody detected with AlexaFluor 568 secondary. (Image provided by Jordan Yaron, Center for Biosignatures Discovery Automation, Arizona State University)

序列:Asc (Tyr-144) phospho-peptide (coupled to KLH) corresponding to amino acid residues surrounding Tyr-144 in mouse Asc. This peptide sequence is highly conserved in human and rat Asc. 

*For more information, see UniProt Accession Q9EPB4

参考文献:

Yu, SH et al. (2019) J Ethnopharmacol. 239:111917. (WB: mouse bone marrow macrophages)
Dubois, EC et al. (2019) PLoS Pathog. 15(4):e1007709. (WB: mouse macrophage)
Furuya, MY et al. (2018) Arthritis Res Ther. 20(1):196. (WB: human neutrophils)
Kwak, SB et al. (2018) Mediators Inflamm. 2018:6054069. (WB: mouse J774A.1, BMDMs)
Hoyt, L.R. et al. (2016) J Immunol. 197:1322. (WB: mouse macrophage, LPS)

订购货号:AP5631

供应商:北京华泰昕生物医疗技术有限公司(ECM Biosciences)

在线订购:AP5631

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