Anti-TrkA/NTRK1 Antibody Picoband® Fluoro488 Conjugated

Neurotrophic tyrosine kinase receptor type 1, also called Trk-A, is a protein that in humans is encoded by the NTRK1 gene. The NTKR1 gene encodes the neurotrophic tyrosine kinase-1 receptor and belongs to a family of nerve growth factor receptors whose ligands include neurotrophins. This gene is mapped to 1q23.1. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, mental retardation and cancer.

A synthetic peptide corresponding to a sequence at the C-terminus of human TrkA, which shares 90.2% amino acid (aa) sequence identity with both mouse and rat TrkA.

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.

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 (PubMed:1850821, PubMed:1849459, PubMed:1281417, PubMed:8325889, PubMed:15488758, PubMed:17196528) . 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 (PubMed:1281417) . 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.

1. Bibel, M., Barde, Y.-A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 14: 2919-2937, 2000. 2. Chuang, H., Prescott, E. D., Kong, H., Shields, S., Jordt, S.-E., Basbaum, A. I., Chao, M. V., Julius, D. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns (4,5) P2-mediated inhibition. Nature 411: 957-962, 2001. 3. Kuruvilla, R., Zweifel, L. S., Glebova, N. O., Lonze, B. E., Valdez, G., Ye, H., Ginty, D. D.A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell 118: 243-255, 2004.