製品: TrkA Antibody
カタログ: AF4689
タンパク質の説明: Rabbit polyclonal antibody to TrkA
アプリケーション: WB
反応性: Human, Mouse, Rat
予測: Pig, Zebrafish, Bovine, Horse, Sheep, Rabbit, Dog, Chicken
分子量: 87kDa; 87kD(Calculated).
ユニプロット: P04629
RRID: AB_2844694

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:500-1:2000
*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(86%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(82%)
クローナリティ:
Polyclonal
特異性:
TrkA Antibody detects endogenous levels of total TrkA.
RRID:
AB_2844694
引用形式: Affinity Biosciences Cat# AF4689, RRID:AB_2844694.
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

gp140trk; High affinity nerve growth factor receptor; High affinity nerve growth factor receptor precursor; MTC; Neurotrophic tyrosine kinase receptor type 1; NTRK1; NTRK1_HUMAN; Oncogene TRK; p14-TrkA; p140 TrkA; p140-TrkA; Slow nerve growth; Trk A; TRK; Trk-A; TRK1; TRK1-transforming tyrosine kinase protein; Tropomyosin-related kinase A; Tyrosine kinase receptor A; Tyrosine kinase receptor;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
発現特異性:
P04629 NTRK1_HUMAN:

Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.

タンパク質配列:
MLRGGRRGQLGWHSWAAGPGSLLAWLILASAGAAPCPDACCPHGSSGLRCTRDGALDSLHHLPGAENLTELYIENQQHLQHLELRDLRGLGELRNLTIVKSGLRFVAPDAFHFTPRLSRLNLSFNALESLSWKTVQGLSLQELVLSGNPLHCSCALRWLQRWEEEGLGGVPEQKLQCHGQGPLAHMPNASCGVPTLKVQVPNASVDVGDDVLLRCQVEGRGLEQAGWILTELEQSATVMKSGGLPSLGLTLANVTSDLNRKNVTCWAENDVGRAEVSVQVNVSFPASVQLHTAVEMHHWCIPFSVDGQPAPSLRWLFNGSVLNETSFIFTEFLEPAANETVRHGCLRLNQPTHVNNGNYTLLAANPFGQASASIMAAFMDNPFEFNPEDPIPVSFSPVDTNSTSGDPVEKKDETPFGVSVAVGLAVFACLFLSTLLLVLNKCGRRNKFGINRPAVLAPEDGLAMSLHFMTLGGSSLSPTEGKGSGLQGHIIENPQYFSDACVHHIKRRDIVLKWELGEGAFGKVFLAECHNLLPEQDKMLVAVKALKEASESARQDFQREAELLTMLQHQHIVRFFGVCTEGRPLLMVFEYMRHGDLNRFLRSHGPDAKLLAGGEDVAPGPLGLGQLLAVASQVAAGMVYLAGLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWYQLSNTEAIDCITQGRELERPRACPPEVYAIMRGCWQREPQQRHSIKDVHARLQALAQAPPVYLDVLG

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
Rabbit
100
Zebrafish
86
Chicken
82
Xenopus
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P04629 基板として

Site PTM Type Enzyme
N95 N-Glycosylation
N121 N-Glycosylation
S123 Phosphorylation
N188 N-Glycosylation
N262 N-Glycosylation
N281 N-Glycosylation
N358 N-Glycosylation
Y490 Phosphorylation
Y496 Phosphorylation P04629 (NTRK1)
Y591 Phosphorylation
Y670 Phosphorylation
S672 Phosphorylation
Y674 Phosphorylation
Y675 Phosphorylation
Y676 Phosphorylation P04629 (NTRK1)
Y680 Phosphorylation P04629 (NTRK1)
Y681 Phosphorylation P04629 (NTRK1)
Y701 Phosphorylation P04629 (NTRK1)
Y729 Phosphorylation
Y757 Phosphorylation
Y785 Phosphorylation
Y791 Phosphorylation P04629 (NTRK1)

PTMs - P04629 酵素として

Substrate Site Source
P04629-3 (NTRK1) Y460 Uniprot
P04629-2 (NTRK1) Y490 Uniprot
P04629 (NTRK1) Y496 Uniprot
P04629-2 (NTRK1) Y670 Uniprot
P04629-2 (NTRK1) Y674 Uniprot
P04629-2 (NTRK1) Y675 Uniprot
P04629 (NTRK1) Y676 Uniprot
P04629 (NTRK1) Y680 Uniprot
P04629 (NTRK1) Y681 Uniprot
P04629 (NTRK1) Y701 Uniprot
P04629-2 (NTRK1) Y751 Uniprot
P04629-3 (NTRK1) Y755 Uniprot
P04629-2 (NTRK1) Y785 Uniprot
P04629 (NTRK1) Y791 Uniprot
P05067 (APP) Y757 Uniprot
P29353-2 (SHC1) Y317 Uniprot
P35222 (CTNNB1) Y142 Uniprot
Q92529-2 (SHC3) Y218 Uniprot
Q92529-2 (SHC3) Y219 Uniprot
Q92529-2 (SHC3) Y256 Uniprot
Q92529-2 (SHC3) Y257 Uniprot
Q92529-2 (SHC3) Y283 Uniprot
Q92529-2 (SHC3) Y301 Uniprot

研究背景

機能:

Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand. Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.

Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.

PTMs:

Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-496 mediates interaction and phosphorylation of SHC1.

N-glycosylated. Isoform TrkA-I and isoform TrkA-II are N-glycosylated.

Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation. Ubiquitination regulates the internalization of the receptor (By similarity).

細胞の位置付け:

Cell membrane>Single-pass type I membrane protein. Early endosome membrane>Single-pass type I membrane protein. Late endosome membrane>Single-pass type I membrane protein. Recycling endosome membrane>Single-pass type I membrane protein.
Note: Rapidly internalized after NGF binding (PubMed:1281417). Internalized to endosomes upon binding of NGF or NTF3 and further transported to the cell body via a retrograde axonal transport. Localized at cell membrane and early endosomes before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with RAPGEF2 at late endosomes.

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 TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors.

サブユニット構造:

Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer. Interacts with SQSTM1; bridges NTRK1 to NGFR. Forms a ternary complex with NGFR and KIDINS220; this complex is affected by the expression levels of KIDINS220 and an increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 (By similarity). Interacts with SH2D1A; regulates NTRK1 (By similarity). Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation. Interacts (phosphorylated) with SH2B1 and SH2B2 (By similarity). Interacts with GRB2. Interacts with PIK3R1. Interacts with FRS2. Interacts with SORT1; may regulate NTRK1 anterograde axonal transport. Interacts with RAB7A (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner (By similarity). Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation (By similarity). Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does not deubiquitinate NTRK1. Interacts with GGA3.

タンパク質ファミリー:

The transmembrane domain mediates interaction with KIDINS220.

The extracellular domain mediates interaction with NGFR.

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

研究領域

· Cellular Processes > Cell growth and death > Apoptosis.   (View pathway)

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

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

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

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

· Human Diseases > Cancers: Overview > Transcriptional misregulation in cancer.

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

· Human Diseases > Cancers: Overview > Central carbon metabolism in cancer.   (View pathway)

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

· Organismal Systems > Sensory system > Inflammatory mediator regulation of TRP channels.   (View pathway)

参考文献

1). Quercetin reverses experimental pulmonary arterial hypertension by modulating the TrkA pathway. EXPERIMENTAL CELL RESEARCH, 2015 (PubMed: 26476374) [IF=3.7]

Application: WB    Species: rat    Sample: rat

Fig. 7. Effect of quercetin on TrkA/AKT pathway signaling in PASMCs. (A) The expression levels of p-TrkA/TrkA and p-AKT/AKT were measured by Western blotting in PASMCs in hypoxia and treated with increasing concentrations of quercetin for 24 h. (B) Results were quantified by densitometry analysis of the bands form (A) and then normalization to GAPDH protein. (C) Effects of NGF, GW441756, and quercetin on the expression of p-TrkA/TrkA and p-AKT/AKT in PASMCs in hypoxia. (D) Densitometric quantification of the bands were shown. (E) The effect of quercetin on PASMCs migration ability under the hypoxia condition treated with or without NGF (50 μg/L). (F) Quantification of the number of cells migrating through the polycarbonate membrane of average of 3 independent experiments. (G) Quantification of the Flow cytometry analysis results to confirm the effects of quercetin on PASMCs apoptosis and (H) cell cycle under the hypoxia condition treated with NGF (50 ug/L). *Po0.05, **Po0.01 compared with control; #Po0.05, ##Po0.01 compared with hypoxia and quercetin treated groups; &Po0.05, &&Po0.01 compared with NGF treated PASMCs.

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