Recombinant Mouse TrkA Fc Chimera Protein, CF Summary
Details of Functionality |
Measured by its ability to inhibit NGF-induced proliferation of TF‑1 human erythroleukemic cells. The ED 50 for this effect is 4-24 ng/mL in the presence of 2 ng/mL of
Recombinant
Mouse beta ‑NGF (Catalog # 1156-NG). |
Source |
Mouse myeloma cell line, NS0-derived mouse TrkA protein Mouse TrkA (Ala34 - Pro418) Accession # Q3UFB7 | IEGRMDP | Mouse IgG2a (Glu98 - Lys330) | N-terminus | | C-terminus | |
|
Accession # |
|
N-terminal Sequence |
Ala34 |
Structure / Form |
Disulfide-linked homodimer
|
Protein/Peptide Type |
Recombinant Proteins |
Purity |
>95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. |
Endotoxin Note |
<0.10 EU per 1 μg of the protein by the LAL method. |
Applications/Dilutions
Dilutions |
|
Theoretical MW |
69 kDa. Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. |
SDS-PAGE |
100 - 125 kDa
|
Packaging, Storage & Formulations
Storage |
Use a manual defrost freezer and avoid repeated freeze-thaw cycles.- 12 months from date of receipt, -20 to -70 °C as supplied.
- 1 month, 2 to 8 °C under sterile conditions after reconstitution.
- 3 months, -20 to -70 °C under sterile conditions after reconstitution.
|
Buffer |
Lyophilized from a 0.2 μm filtered solution in PBS. |
Purity |
>95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. |
Reconstitution Instructions |
Reconstitute at 500 μg/mL in PBS. |
Notes
This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.
Alternate Names for Recombinant Mouse TrkA Fc Chimera Protein, CF
Background
Tropomyocin
receptor kinase A (TrkA), also named Neurotrophic tyrosine kinase receptor type
1 (NTRK3) is a member of a nerve growth factor tyrosine kinase receptor
family. There are three members of the
Trk family, TrkA, TrkB and TrkC, and they bind a group of structurally related,
secreted proteins termed neurotrophins, which play an important role in the
development and function of the nervous system. The Trk family shares a
conserved structural motif consisting of two cysteine-rich domains, a cluster
of three leucine-rich motifs, and two immunoglobulin-like domains in the
extracellular region, a single transmembrane domain and an intracellular
tyrosine kinase domain (3). Natural
splice variants of the different Trks, lacking the first cysteine-rich domain,
the first and second or all three of the leucine-rich motifs, or the tyrosine
kinase domain, have been described (4). Mature mouse TrkA consists of a 383
amino acid (aa) extracellular domain (ECD) which shares 79% and 93% aa
identity with human and rat TrkA, respectively. Each Trk family member exhibits
different ligand specificities: TrkA binds NGF and NT-3, TrkB binds BDNF, NT-3
and NT-4/5, and TrkC only binds NT-3 (1, 2). The biological activities of the
neurotrophins are mediated by binding to and activating two unrelated receptor
types: the p75 neurotrophin receptor (p75NTR) and the Trk family receptors (1, 2). P75NTR is a member of the tumor necrosis factor receptor superfamily
(TNFRSF) and has been designated TNFRSF16. It binds all neurotrophins with
low-affinity to transduce cellular signaling pathways that synergize or
antagonize those activated by the Trk receptors. Several TrkA isoforms exist, two
of which differ only by a 6-amino acid insertion in their extracellular domain
(3). The longer TrkA isoform is the only isoform expressed within neuronal
tissues whereas the shorter TrkA is expressed mainly in non-neuronal tissues (3).
Trk receptor interactions with NGF play major roles in the development of the
sympathetic nervous system, and TrkA, specifically, is essential to the
survival of sympathetic neurons in vivo (4). NGF activates retrograde
transport of TrkA endosomes for association with actin-modulatory proteins to
promote F-actin disassembly, enabling their maturation into transport-competent
signaling endosomes (1). Inhibition of the Trk receptors may have several
therapeutic implications (5). Injection of a TrkA inhibitor in patients with
knee osteoarthritis resulted in sustained pain improvement in a single center
trial (6). Another inhibitor showed a significant reduction in psoriatic
pruritus, which occurs via a Trka-dependent mechanism (7).
- Harrington, A. et al. (2011) Cell. 146(3):421.
- Smeyne, R. et al. (1994) 368(6468):246.
- Barker, P. et al. (1992) 268(20):15150.
- Fagan, A. et al. (1996) J Neurosci. 16(19):6208.
- Yan, W. et al. (2019) J Med. Chem. 62(4):1731.
- Krupka, E. et al. (2019) Osteoarthr Cartil. DOI: 10:1016.
- Yosipovitch, R. et al. (2015) Acta Derm Venereol. 95.
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