|Detection of TrkA in Human Blood Monocytes by Flow Cytometry. Human peripheral blood monocytes were stained with Mouse Anti-Human CD14 PE‑conjugated Monoclonal Antibody (Catalog # FAB3832P) and either (A) Mouse Anti-Human TrkA Alexa Fluor® 700‑conjugated Monoclonal Antibody (Catalog # FAB1751N) or (B) Mouse IgG1 Alexa Fluor 700 Isotype Control (Catalog # IC002N). View our protocol for Staining Membrane-associated Proteins.|
TrkA, the product of the proto-oncogene trk, is a member of the neurotrophic tyrosine kinase receptor family that has three members. TrkA, TrkB, and TrkC. TrkA binds NGF and NT-3, while TrKB binds NT-4 and BDNF, and TrkC binds NT-3. All Trk family proteins share a conserved complex subdomain organization consisting of two cysteine-rich segments, a cluster of three leucine-rich motifs, and two immunoglobulin-like domains in the extracellular region, coupled to an intracellular region that contains a tyrosine kinase domain. Two distinct TrkA isoforms that differ by virtue of a 6-amino acid (aa) insertion after Pro392 in their extracellular domain have been identified. The longer TrkA isoform is the only isoform expressed within neuronal tissues, whereas the shorter TrkA is expressed mainly in non-neuronal tissues. A third TrkA variant is expressed by neural stem cells. This isoform shows a Val substitution for aa 194-283 and an absence of the aforementioned 6 aa insert. NGF binds to TrkA with low affinity and activates its cytoplasmic kinase, initiating a signaling cascade that mediates neuronal survival and differentiation. Higher affinity binding of NGF requires the coexpression of TrkA with the p75 NGF receptor (NGF R), a member of the tumor necrosis factor receptor superfamily. NGF R binds all neurotrophins with low affinity and modulates Trk activity as well as alters the specificity of Trk receptors for their ligands. NGF R can also mediate cell death when expressed independent of Trk. Over aa 33-407, human TrkA shares 79% aa sequence identity with mouse TrkA.