製品: Phospho-IRAK1 (Thr387) Antibody
カタログ: AF8009
タンパク質の説明: Rabbit polyclonal antibody to Phospho-IRAK1 (Thr387)
アプリケーション: WB IHC
Cited expt.: WB
反応性: Human, Mouse, Rat
予測: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog
分子量: 77kDa; 77kD(Calculated).
ユニプロット: P51617
RRID: AB_2840072

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:1000-3000, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat
予測:
Pig(91%), Zebrafish(100%), Bovine(91%), Horse(91%), Sheep(91%), Rabbit(91%), Dog(91%)
クローナリティ:
Polyclonal
特異性:
Phospho-IRAK1 (Thr387) Antibody detects endogenous levels of IRAK1 only when phosphorylated at Thr387.
RRID:
AB_2840072
引用形式: Affinity Biosciences Cat# AF8009, RRID:AB_2840072.
コンジュゲート:
Unconjugated.
精製:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

AA48924; Il1rak; Interleukin 1 receptor associated kinase 1; Interleukin-1 receptor-associated kinase 1; IRAK; IRAK-1; Irak1; IRAK1-S; IRAK1_HUMAN; mPLK; OTTHUMP00000026014; OTTHUMP00000026015; OTTHUMP00000026020; OTTHUMP00000180621; Pelle; Pelle homolog; Pelle-like protein kinase; Plpk;

免疫原

免疫原:

A synthesized peptide derived from human IRAK1 around the phosphorylation site of Thr387.

Uniprot:
遺伝子(ID):
発現特異性:
P51617 IRAK1_HUMAN:

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.

タンパク質配列:
MAGGPGPGEPAAPGAQHFLYEVPPWVMCRFYKVMDALEPADWCQFAALIVRDQTELRLCERSGQRTASVLWPWINRNARVADLVHILTHLQLLRARDIITAWHPPAPLPSPGTTAPRPSSIPAPAEAEAWSPRKLPSSASTFLSPAFPGSQTHSGPELGLVPSPASLWPPPPSPAPSSTKPGPESSVSLLQGARPFPFCWPLCEISRGTHNFSEELKIGEGGFGCVYRAVMRNTVYAVKRLKENADLEWTAVKQSFLTEVEQLSRFRHPNIVDFAGYCAQNGFYCLVYGFLPNGSLEDRLHCQTQACPPLSWPQRLDILLGTARAIQFLHQDSPSLIHGDIKSSNVLLDERLTPKLGDFGLARFSRFAGSSPSQSSMVARTQTVRGTLAYLPEEYIKTGRLAVDTDTFSFGVVVLETLAGQRAVKTHGARTKYLKDLVEEEAEEAGVALRSTQSTLQAGLAADAWAAPIAMQIYKKHLDPRPGPCPPELGLGLGQLACCCLHRRAKRRPPMTQVYERLEKLQAVVAGVPGHSEAASCIPPSPQENSYVSSTGRAHSGAAPWQPLAAPSGASAQAAEQLQRGPNQPVESDESLGGLSAALRSWHLTPSCPLDPAPLREAGCPQGDTAGESSWGSGPGSRPTAVEGLALGSSASSSSEPPQIIINPARQKMVQKLALYEDGALDSLQLLSSSSLPGLGLEQDRQGPEESDEFQS

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Zebrafish
100
Pig
91
Horse
91
Bovine
91
Sheep
91
Dog
91
Rabbit
91
Xenopus
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

研究背景

機能:

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.

PTMs:

Following recruitment on the activated receptor complex, phosphorylated on Thr-209, probably by IRAK4, resulting in a conformational change of the kinase domain, allowing further phosphorylations to take place. Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity.

Polyubiquitinated by TRAF6 after cell stimulation with IL-1-beta by PELI1, PELI2 and PELI3. Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'. Ubiquitination promotes interaction with NEMO/IKBKG. Also sumoylated; leading to nuclear translocation.

細胞の位置付け:

Cytoplasm. Nucleus. Lipid droplet.
Note: Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.

タンパク質ファミリー:

The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation.

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.

研究領域

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > NF-kappa B signaling pathway.   (View pathway)

· Human Diseases > Infectious diseases: Bacterial > Pertussis.

· Human Diseases > Infectious diseases: Parasitic > Leishmaniasis.

· Human Diseases > Infectious diseases: Parasitic > Chagas disease (American trypanosomiasis).

· Human Diseases > Infectious diseases: Parasitic > Toxoplasmosis.

· Human Diseases > Infectious diseases: Bacterial > Tuberculosis.

· Human Diseases > Infectious diseases: Viral > Measles.

· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.

· Organismal Systems > Immune system > Toll-like receptor signaling pathway.   (View pathway)

· Organismal Systems > Nervous system > Neurotrophin signaling pathway.   (View pathway)

参考文献

1). S100A14 suppresses metastasis of nasopharyngeal carcinoma by inhibition of NF-kB signaling through degradation of IRAK1. Oncogene, 2020 (PubMed: 32555330) [IF=6.9]

Application: WB    Species: Human    Sample: nasopharyngeal mucosa and nasopharyngeal carcinoma

Fig. 5 S100A14 promotes ubiquitin–proteasome-mediated degradation of IRAK1. a Immunoblotting analysis of P-IRAK1 (T387) and IRAK1 protein levels in the S100A14 overexpressing cells and S100A14 knocked-down cells.

2). The novel mechanism of human norovirus induced diarrhea: Activation of PKD2 caused by HuNoVs destroyed AQP3 expression through AP2γ in intestinal epithelial cells. Life sciences, 2024 (PubMed: 38103725) [IF=5.2]

3). Ficolin-A/2, acting as a new regulator of macrophage polarization, mediates the inflammatory response in experimental mouse colitis. IMMUNOLOGY, 2017 (PubMed: 28380665) [IF=4.9]

Application: WB    Species: mouse    Sample:

Figure 7. FCN-A promoted the M1 polarization of BMDMs through a TLR4/MyD88-dependent pathway in vitro. (a) The protein expressions of the purified GST-FCN-A and GST were determined by SDS-PAGE. (b) The extracted membrane proteins from RAW264.7 cells were incubated with the purified GST-FCN-A or GST proteins. Co-IP analysis of the interaction between TLR4 of macrophage and GST-FCN-A was performed by using anti-TLR4. Rabbit IgG was used as a negative control in co-IP. (c, e) BMDMs, isolated from WT, TLR4-/- or MyD88-/- mice, were stimulated with FCN-A (10g/mL) for 24 h, then the expressions of iNOS and Arg-1 from BMDMs were examined by Western blot analysis. (d, f) The levels of pro-inflammatory cytokines IL-1in cell lysates, and secreted IL-6, TNF- were detected by ELISA. (g, h) Western blot analysis of p-IRAK1, p-p65, p-ERK1/2, and p-JNK in the BMDM lysates of TLR4-/-, MyD88-/- or WT after stimulation with FCN-A for 0-45 min. In d and f, values are mean ± [SEM] from three independent experiments.

4). Optimized new Shengmai powder ameliorates myocardial fibrosis in rats with heart failure by inhibition of the MAPK signaling pathway. Journal of ethnopharmacology, 2024 (PubMed: 37739104) [IF=4.8]

Application: WB    Species: Rat    Sample:

Fig. 8. Effects of ONSMP on JNK1/2 signaling pathway. (A) Representative western blotting bands of p-IRAK4, IRAK4, p-IRAK1, IRAK1, p-TAK1, TAK1, p-MKK4, MKK4, p-MKK7, MKK7, p-JNK1/2, JNK1/2, MD2, TLR4, MyD88, and c-Jun in the myocardium, with vinculin as internal reference. (B–K) Statistical graphs of p-IRAK4/IRAK4, p-IRAK1/IRAK1, p-TAK1/TAK1, p-MKK4/MKK4, p-MKK7/MKKK7, p-JNK1/2/JNK1/2, MD2, TLR4, MyD88, and c-Jun (n = 3). Data are presented as mean ± SEM. nsP > 0.05; ▲▲P < 0.01 vs the sham; *P < 0.05, **P < 0.01 vs the model; #P < 0.05, ##P < 0.01 vs the ONSMP-L; ※P < 0.05, ※※P < 0.01 vs the ONSMP-M.

5). Artemisinin attenuates perinatal inflammation and consequent oxidative stress in oligodendrocyte precursor cells by inhibiting IRAK-4 and IRAK-1. International Immunopharmacology, 2024 [IF=4.8]

Application: WB    Species: Rat    Sample: OPCs

Fig. 4. LPS-induced activation of the IRAK-4/IRAK-1/NF-κB signalling pathway in OPCs was inhibited by ART. a, b, c, d Western blotting was used to quantify the protein levels of p-IRAK-4, IRAK-4, p-IRAK-4/IRAK-4, p-IRAK-1, IRAK-1, p-IRAK-1/IRAK-1, phospho-NF-kB p65, NF-κB p65, and phospho-NF-kB p65/NF-κB p65 in 4 groups (the Ctrl, ART, LPS, and LPS + ART groups). The data are expressed as the means ± SEMs (n = 6/group) (*p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001).

Application: IF/ICC    Species: Rat    Sample: OPCs

Fig. 5. ART reduces NF-κB nuclear aggregation after LPS stimulation. a, b, c Immunofluorescence was used to compare the relative fluorescence of p-IRAK-4 (red) and p-IRAK-1 (red) in OPCs across several groups (the Ctrl, ART, LPS, and LPS + ART groups), and the proportion (%) of nuclear NF-κB p65 (red) was determined. DAPI staining is shown in blue. Scale bar = 50 μm. The data are presented as the means ± SEMs (n = 6). ****P < 0.0001 versus the indicated groups.

6). Isorhynchophylline ameliorates paraquat-induced acute kidney injury by attenuating oxidative stress and mitochondrial damage via regulating toll-interacting expression. TOXICOLOGY AND APPLIED PHARMACOLOGY, 2021 (PubMed: 33838153) [IF=3.3]

Application: WB    Species: Rat    Sample: kidney tissues

Fig. 4. Effects of INR on Tollip expression and mitochondrial damage in kidney tissues of PQ-intoxicated rats. (A) Tollip expression in kidney tissues was detected by immunohistochemistry. Scale bars: 200 μm (100× magnification) and 50 μm (400× magnification). (B, C) Western blot showed the expression of Tollip, p-IRAK1 and IRAK1 in kidney tissues. (D, E) Western blot evaluated the release of Cytochrome C from mitochondria into cytosol. ###p < 0.001 vs. PQ.

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