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NTRK1

Products

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Neurotrophic receptor tyrosine kinase 1 (NTRK1) which is also referred to as tropomyosin receptor kinase A (TrkA), is approximately 140 kDa member of the family of trkreceptor Tyr kinasesthat are characterized by their abilityto bind with and activate different forms. It has an LRR motif in the extracellular region and is flanked by two clusters of cysteines, followed by two tandem immunoglobulin-like domains (IgC1 and IgC2) that together provide a high-affinity binding interface for nerve growth factor (NGF). The ATP-binding pocket and catalytic residues necessary for autophosphorylation and propagation of downstream signaling reside within the intracellular kinase domain. NTRK1 is mainly limited to neuronal tissues under physiological conditions, where it mediates the survival, differentiation and axonal growth of NGF-dependent sensory and sympathetic neurons. Ligand binding induces receptor homodimerization, trans-autophosphorylation of key tyrosine residues as well recruiting adapter proteins including Shc Grb2 and PLCγ. These interactions trigger the canonical RAS/MAPK, PI3K/AKT, and PLCγ-mediated PKC signaling cascades that together control neuronal differentiation/development (neurogenesis), synaptic plasticity leading to cognitive functions related to training paradigms such as memory retention or conditioned responses after reward-based learning in mice under behavior analyses testing for retaliation/counter-defense mechanisms producing nociception. The precision of this signaling axis is critical for normal peripheral nervous system development and homeostasis.

Fig.1 NTRK1 in different cancers. (OA Literature)Fig.1 NTRK gene fusions in cancers.1

NTRK1 Protein Function: From Neural Development to Oncogenic Transformation

The biological relevance of NTRK1 encompasses development, neurobiology and malignancy:

  • Neuronal Survival and Nociception: The high-affinity receptor for NGF, NTRK1 is essential in the development/survival of small-diameter nociceptive neurons as well as sympathetic postganglionic neurons. The loss of NTRK1 function prevents NGF-dependent signaling, triggering apoptotic demise in these neurotrophic populations that normally are destined to survive embryogenesis.
  • Oncogenic Gene Fusions: In opposition to its physiological role, chromosomal aberrations involving NTRK1 give rise to powerful oncogenes. Gene fusions place the 3' region of NTRK1 (bearing a kinase domain and transmembrane segment) in juxtaposition to diverse partner genes with either a private tropism or more public feature.
  • Therapeutic Targeting and Resistance: The clinical tenure of NTRK1 fusions as clinically relevant oncogenic drivers has spurred the development of targeted TRK inhibitors. First-generation agents larotrectinib and entrectinib have shown over 75% histology-agnostic response rates in NTRK fusion-positive cancers, with subsequent regulatory approval in multiple jurisdictions. Acquired resistance mediated by kinase domain mutations (most prominently the solvent-front mutation G595R) and the gatekeeper mutation.

NTRK1 Membrane Protein Product

Advance your neurobiology and disease-related research with our recombinant NTRK1 membrane protein products. The multi-domain extracellular architecture, transmembrane topology, and kinase-dependent conformational dynamics of NTRK1 present distinct considerations for protein production and experimental design. We provide wild-type and engineered NTRK1 research constructs suitable for a range of applications, including structural studies, NGF-binding research, antibody development and characterization, and investigation of receptor kinase function and inhibition. Available species, fusion constructs, sequence variants, expression formats, and functional characteristics should be determined according to the corresponding product information and supporting data.

NTRK1 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

NTRK1 Stable Cell Line Product

Reproducible and reliable cellular models are essential to dissect NTRK1-driven biology and assess drug candidates. Stable cell lines expressing either wild-type or oncogenic alleles of human, mouse and rat NTRK1 (available from our B2B Biorepository) with concomitant modulation of endogenous expression for loss-of-function experiments. These platforms maximise throughput for TRK inhibitor screening, downstream phosphorylation assays, neurite outgrowth quantification and fusion protein internalisation studies to provide the key experimental reproducibility necessary in multi-step projects.

NTRK1 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

NTRK1 Recombinant Antibody Product

We have developed a high-affinity recombinant antibody portfolio targeting NTRK1 that is optimized for challenging research applications. These antibodies engineered in accordance with use of advanced recombinant technologies provide greater specificity, sensitivity and consistency from batch to batch than polyclonal (traditional) antibodies. Validated for use in WB, ELISA, FCM, IF/ICC/IHC/IP Our NTRK1 recombinant antibodies can detect & quantify your target proteins in neuronal lysis buffers as well as human tumor biopsy and transfected membranes.

NTRK1 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom NTRK1 Membrane Protein and Antibody Discovery Services

In addition to products in our catalog, we also provide tailored custom services for membrane protein and antibody discovery and development:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous NTRK1 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Do you offer stable cell lines that co-express NTRK1 and its downstream adaptor SHC1 for continuous modeling of neurotrophin signal propagation and neurite outgrowth?

    Yes, we reported stable lines expressing both full-length NTRK1 and SHC1 from distinct loci constitutively. Batches are accompanied by characterization of NGF-stimulated neurite outgrowth and downstream ERK phosphorylation that allows ongoing mechanistic investigations without the need to repeat transient transfection.

  2. Is your recombinant NTRK1 ectodomain in a carrier-free format suitable for direct amine coupling to biosensor chips to measure NGF binding kinetics and competition assays?

    Yes, the protein is prepared in a defined buffer free of amines and endotoxin that maintains physiological pH leading to conservation of its native immunoglobulin-like fold.

  3. Are your NTRK1 products intended for clinical or diagnostic purposes?

    No all NTRK1 products & services are for Research use only, and are not intended for clinical diagnosis, prevention, treatment, or cure of any disease.

  4. Do you provide stable cell lines with inducible NTRK1 expression?

    Absolutely. Cells engineered by our team typically include tetracycline-inducible systems, along with lines co-expressing NTRK1 and TPM3 or LMNA combinations or truncated reporter constructs to facilitate a thorough pathway analysis. We look forward to having a more detailed conversation about the expression architecture and phenotypic criteria you are looking for.

Reference
  1. Zito Marino, Federica, et al. "NTRK fusions, from the diagnostic algorithm to innovative treatment in the era of precision medicine." International journal of molecular sciences 21.10 (2020): 3718. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms21103718
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