製品: LRP6 Antibody
カタログ: DF2995
タンパク質の説明: Rabbit polyclonal antibody to LRP6
アプリケーション: WB IHC
Cited expt.: WB, IHC
反応性: Human, Mouse, Rat
予測: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
分子量: 180 KD; 180kD(Calculated).
ユニプロット: O75581
RRID: AB_2840974

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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(100%), Zebrafish(80%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(100%)
クローナリティ:
Polyclonal
特異性:
LRP6 Antibody detects endogenous levels of total LRP6.
RRID:
AB_2840974
引用形式: Affinity Biosciences Cat# DF2995, RRID:AB_2840974.
コンジュゲート:
Unconjugated.
精製:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
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

ADCAD2; C030016K15Rik; Cd; FLJ90062; FLJ90421; Low density lipoprotein receptor related protein 6; Low-density lipoprotein receptor-related protein 6; LRP-6; LRP6; LRP6_HUMAN; OTTHUMP00000238979; OTTHUMP00000238980; OTTHUMP00000238982;

免疫原

免疫原:

A synthesized peptide derived from human LRP6, corresponding to a region within C-terminal amino acids.

Uniprot:
遺伝子(ID):
発現特異性:
O75581 LRP6_HUMAN:

Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

タンパク質配列:
MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS

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

研究背景

機能:

Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity).

PTMs:

Dual phosphorylation of cytoplasmic PPPSP motifs sequentially by GSK3 and CK1 is required for AXIN1-binding, and subsequent stabilization and activation of beta-catenin via preventing GSK3-mediated phosphorylation of beta-catenin. Phosphorylated, in vitro, by GRK5/6 within and outside the PPPSP motifs. Phosphorylation at Ser-1490 by CDK14 during G2/M phase leads to regulation of the Wnt signaling pathway during the cell cycle. Phosphorylation by GSK3B is induced by RPSO1 binding and inhibited by DKK1. Phosphorylated, in vitro, by casein kinase I on Thr-1479.

Undergoes gamma-secretase-dependent regulated intramembrane proteolysis (RIP). The extracellular domain is first released by shedding, and then, through the action of gamma-secretase, the intracellular domain (ICD) is released into the cytoplasm where it is free to bind to GSK3B and to activate canonical Wnt signaling.

Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.

Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.

N-glycosylation is required for cell surface location.

細胞の位置付け:

Cell membrane>Single-pass type I membrane protein. Endoplasmic reticulum. Membrane raft.
Note: On Wnt signaling, undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-signalsomes. Chaperoned to the plasma membrane by MESD (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:

Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

タンパク質ファミリー:

The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1.

The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.

Belongs to the LDLR family.

研究領域

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

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

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Breast cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

参考文献

1). Betulinic acid Attenuated Bleomycin-induced Pulmonary Fibrosis by Effectively Intervening Wnt/β-catenin Signaling. PHYTOMEDICINE, 2021 (PubMed: 33341025) [IF=6.7]

Application: WB    Species: Mice    Sample: Mlg and PPF cells

Fig. 5. BA promoted β-catenin phosphorylation and inhibited the combination of LRP6 and Wnt3a. Mlg and PPF cells were maintained in the presence of BA (5, 10 and 20 μM) for 2 h and then treated with Wnt3a (100 ng/ml) for another 2 h. (A-B) The expression of pS33/37/T41-β-catenin, pT41/S45-β-catenin and β-catenin in (A) Mlg and (B) PPF cells were evaluated using immunoblot assay. Densitometric analysis of p-β-catenin using β-catenin as the internal reference showed beside the blots and "Fold change" refers to the ratio of the gray analysis value of p-β-catenin to the gray analysis value of β-catenin multiplied by 100%. (C-D) Immunoblot analysis of DVL2, p-LRP6, total LRP6 and GAPDH in (C) Mlg and (D) PPF cells of different group. The immunoblots of p-LRP6 were quantified by densitometry using LRP6 as the internal reference. (E) Mlg cells were treated with BA (10 μM) for 2 h and then added Wnt3a (100 ng/ml) for additional 1 h. The protein levels of Wnt3a and LRP6 were detected by western blot. Results are shown as mean ± SEM, n = 3.

2). Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma. Oncotarget, 2017 (PubMed: 28423559)

Application: IHC    Species: mouse    Sample:

Figure 5: The expression of β-catenin, LRP6, and p-LRP by immunohistochemistry staining in xenograft tissues. The positive expressing proteins appeared brown in color.The results showed that rottlerin down-regulated the expression of β-catenin, LRP6, and p-LRP compared with the control and DMSO-treated groups (*p < 0.05) in vivo. The suppression was stronger in the higher dosetreated group (rottlerin 4 mg/kg) than the lower dose-treated group (rottlerin 2 mg/kg; **p < 0.05).

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