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  4. Phospho-NTRK1 (Tyr757) Antibody

Phospho-NTRK1 (Tyr757) Antibody

  • 货号：
    CSB-PA271642
  • 规格：
    ￥2454
  • 图片：
    • Immunohistochemical analysis of paraffin-embedded human brain tissue using Trk A (Phospho-Tyr757) antibody (left)or the same antibody preincubated with blocking peptide (right).
  • 其他：

产品详情

  • 产品名称：
    Rabbit anti-Homo sapiens (Human) NTRK1 Polyclonal antibody
  • Uniprot No.：
    P04629
  • 基因名：
  • 别名：
    NTRK1; MTC; TRK; TRKA; High affinity nerve growth factor receptor; Neurotrophic tyrosine kinase receptor type 1; TRK1-transforming tyrosine kinase protein; Tropomyosin-related kinase A; Tyrosine kinase receptor; Tyrosine kinase receptor A; Trk-A; gp140trk; p140-TrkA
  • 宿主：
    Rabbit
  • 反应种属：
    Human,Mouse
  • 免疫原：
    Peptide sequence around phosphorylation site of tyrosine 757 (E-V-Y(p)-A-I) derived from Human Trk A.
  • 免疫原种属：
    Homo sapiens (Human)
  • 克隆类型：
    Polyclonal
  • 纯化方式：
    Antibodies were produced by immunizing rabbits with synthetic phosphopeptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific phosphopeptide. Non-phospho specific antibodies were removed by chromatogramphy usi
  • 浓度：
    It differs from different batches. Please contact us to confirm it.
  • 产品提供形式：
    Liquid
  • 应用范围：
    ELISA,IHC
  • 推荐稀释比：
    Application Recommended Dilution
    IHC 1:50-1:100
  • Protocols：
  • 储存条件：
    Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
  • 货期：
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

产品评价

靶点详情

  • 功能：
    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. 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.
  • 基因功能参考文献：
    1. Two novel compound heterozygous variants of NTRK1 (c.632T > A and c.1253_1254delTC) were identified in a pair of Chinese identical twins with Congenital Insensitivity to Pain and Anhidrosis. PMID: 30461622
    2. The above results suggest that rutin preconditioning ameliorates cerebral I/R injury in OVX rats through ER-mediated BDNF-TrkB and NGF-TrkA signaling. PMID: 29420916
    3. The TrkA peptide is competitive for metal binding with analogous peptides due to the N-terminal domain of NGF. These data provide cues for future exploration of the effect of metal ions on the activity of the NGF and its specific cellular receptor. PMID: 30103559
    4. The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target. PMID: 30134855
    5. that lipofibromatosis-like tumour represents a novel entity of NTRK1-associated neoplasms PMID: 29958731
    6. System xC(-)-mediated TrkA activation therefore presents a promising target for therapeutic intervention in cancer pain treatment. PMID: 29761734
    7. Results identified two known splice-site mutations, one known nonsense mutation and one novel missense mutation in three congenital insensitivity to pain with anhidrosis (CIPA) pedigrees. These findings expanded the spectrum of the NTRK1 mutations associated with CIPA patients, provided additional clues for the phenotype-genotype relationship beneath CIPA. PMID: 30201336
    8. 27 mutations in NTRK1 from Congenital insensitivity to pain with anhidrosis cohort, including 15 novel mutations, are reported. PMID: 29770739
    9. NTRK1 was upregulated in 80% of head and neck squamous carcinoma tissue. PMID: 29904026
    10. TRKA expression can be found in 1.6% of solid tumours and can be paralleled by NTRK1 gene rearrangements or mostly copy number gain PMID: 29802225
    11. These results suggest that polymorphisms in NTRK1 play an important role in pain sensitivity in young Han Chinese women PMID: 29054434
    12. We developed a comprehensive model of acquired resistance to NTRK inhibitors in cancer with NTRK1 rearrangement and identified cabozantinib as a therapeutic strategy to overcome the resistance PMID: 28751539
    13. TrkA plays an important role in the pathogenesis of NPM-ALK(+) T-cell lymphoma. PMID: 28557340
    14. Results show frequent BRCA2, EGFR, and NTRK1/2/3 mutations in mismatch repair-deficient colorectal cancers , sugggesting personalized medicine strategies to treat the patients with advanced disease who may have no remaining treatment options PMID: 28591715
    15. novel deletional mutation has enriched the spectrum of NTRK1 mutations PMID: 28981924
    16. This study identify four novel NTRK1 mutations (IVS14+3A>T, p.Ser235*, p.Asp596Asn, and p.Leu784Serfs*79) and demonstrate that they are pathologic mutations using an mRNA splicing assay and an NTRK autophosphorylation assay. PMID: 28177573
    17. Report a novel mechanism for the TRAIL-induced apoptosis of TrkAIII expressing NB cells that depends upon SHP/Src-mediated crosstalk between the TRAIL-receptor signaling pathway and TrkAIII. PMID: 27821809
    18. This show evidence of variation in plasmatic monocytic TrkA expression during the progression of dementia. PMID: 27802234
    19. TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples. TrkA expression was independent of histologic subtypes but associated with lymph node metastasis, suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. PMID: 29037860
    20. phenotypes, as well as both recurrent and novel mutations in NTRK1 in 2 Chinese patients with CIPA PMID: 28192073
    21. we conclude that complete abolition of TRKA kinase activity is not the only pathogenic mechanism underlying HSAN IV. PMID: 27676246
    22. Nine patients have been reported from nine unrelated families with hereditary sensory and autonomic neuropathy IV due to various mutations in NTRK1, five of which are novel. PMID: 28328124
    23. Data suggest that kinase domains of neurotrophin receptor isoforms, TRKA, TRKB, and TRKC, exhibit a bulky phenylalanine gatekeeper, leading to a small and unattractive back pocket/binding site for antineoplastic kinase inhibitors. [REVIEW] PMID: 28215291
    24. Pan-Trk immunohistochemistry is a time-efficient and tissue-efficient screen for NTRK fusions, particularly in driver-negative advanced malignancies and potential cases of secretory carcinoma and congenital fibrosarcoma. PMID: 28719467
    25. analysis of NTRK1 transcripts in peripheral blood cells of the patient revealed an influence of the variant on mRNA splicing. The C>A transversion generated a novel splice-site, which led to the incorporation of 10 intronic bases into the NTRK1 mRNA and consequently to a non-functional gene product. PMID: 27184211
    26. NTRK fusions occur in a subset of young patients with mesenchymal or sarcoma-like tumors at a low frequency PMID: 28097808
    27. A novel nonsense mutation and a known splice-site mutation were detected in NTRK1 in two siblings and were shown to be associated with congenital insensitivity to pain with anhidrosis. PMID: 28345382
    28. NTRK1 gene fusion in spitzoid neoplasms results in tumors with Kamino bodies and were typically arranged in smaller nests with smaller predominantly spindle-shaped cells, occasionally forming rosettes. PMID: 27776007
    29. Results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling lipofibromatosis (LPF), but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors. PMID: 27259011
    30. This review highlights treatment options, including clinical trials for ROS1 rearrangement, RET fusions, NTRK1 fusions, MET exon skipping, BRAF mutations, and KRAS mutations. PMID: 27912827
    31. ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine-binding (PTB) domain. PMID: 28213521
    32. TrkA misfolding and aggregation induced by some Insensitivity to Pain with Anhidrosis mutations disrupt the autophagy homeostasis causing neurodegeneration. PMID: 27551041
    33. USP36 actions extend beyond TrkA because the presence of USP36 interferes with Nedd4-2-dependent Kv7.2/3 channel regulation. PMID: 27445338
    34. Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients PMID: 26459250
    35. High NTRK1 expression is associated with colon cancer. PMID: 26716414
    36. TrkA immunohistochemistry is an effective, initial screening method for NTRK1 rearrangement detection in the clinic. PMID: 26472021
    37. This work identifies GGA3 as a key player in a novel DXXLL-mediated endosomal sorting machinery that targets TrkA to the plasma membrane, where it prolongs the activation of Akt signaling and survival responses. PMID: 26446845
    38. Data show that p.G595R and p.G667C TRKA mutations drive acquired resistance to entrectinib in colorectal cancers carrying NTRK1 rearrangements. PMID: 26546295
    39. Two key biological processes for progressive hearing loss, TrkA signaling pathway and EGF receptor signaling pathway were significantly and differentially enriched by the two sets of allele-specific target genes of miR-96. PMID: 26564979
    40. Report novel variant of myo/haemangiopericytic sarcoma with recurrent NTRK1 gene fusions. PMID: 26863915
    41. TrkA as a candidate oncogene in malignant melanoma and support a model in which the NGF-TrkA-MAPK pathway may mediate a trade-off between neoplastic transformation and adaptive anti-proliferative response. PMID: 26496938
    42. IL-13 confers epithelial cell responsiveness to NGF by regulating NTRK1 levels by a transcriptional and epigenetic mechanism and that this process likely contributes to allergic inflammation. PMID: 25389033
    43. findings suggest that Cbl-b limits NGF-TrkA signaling to control the length of neurites. PMID: 25921289
    44. mRNA expression of NTRK1 genes was higher in low-grade gliomas vs. high-grade and control samples. Poor survival was associated with NTRK1 mRNA. Promoter methylation does not regulate NTRK1 genes in glioma. PMID: 24840578
    45. Translocations in the NTRK1 gene are recurring events in colorectal cancer, although occurring at a low frequency (around 0.5%). PMID: 26001971
    46. Findings have implications for understanding the mature and less malignant neuroblastoma phenotype associated with NTRK1 expression, and could assist the development of new therapeutic strategies for neuroblastoma differentiation PMID: 25361003
    47. TrkA expression in neurons was found to be regulated at the gene promoter level by Bex3 protein. PMID: 25948268
    48. Causative role for M379I and R577G NTRK1 mutations in melanoma development is highly unlikely. PMID: 24965840
    49. Increased NTRK1 expression is associated with spontaneous abortions. PMID: 24825909
    50. Data indicate how the neurotrophins function through tyrosine kinase receptors TrkC and TrkA. PMID: 24603864

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  • 相关疾病：
    Congenital insensitivity to pain with anhidrosis (CIPA)
  • 亚细胞定位：
    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.
  • 蛋白家族：
    Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily
  • 组织特异性：
    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.
  • 数据库链接：

    HGNC: 8031

    OMIM: 164970

    KEGG: hsa:4914

    STRING: 9606.ENSP00000431418

    UniGene: Hs.406293