Tropomyosin receptor kinase A

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Tropomyosin Receptor Kinase A

Diagram of Tropomyosin Receptor Kinase A

Tropomyosin receptor kinase A (TrkA) is a protein that in humans is encoded by the NTRK1 gene. TrkA is a member of the neurotrophin receptor family, which are tyrosine kinase receptors. These receptors are critical for the development and function of the nervous system.

Structure

TrkA is a transmembrane receptor with an extracellular domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. The extracellular domain is responsible for binding to its ligand, nerve growth factor (NGF), while the intracellular domain is involved in signal transduction.

Function

TrkA is primarily known for its role in the development and survival of neurons. It is activated by binding to NGF, which leads to receptor dimerization and autophosphorylation of tyrosine residues in the intracellular domain. This activation triggers several downstream signaling pathways, including the MAPK/ERK pathway, the PI3K/AKT pathway, and the PLC_ pathway. These pathways are involved in promoting neuronal survival, differentiation, and synaptic plasticity.

Clinical Significance

Mutations in the NTRK1 gene can lead to a rare genetic disorder known as congenital insensitivity to pain with anhidrosis (CIPA), which is characterized by the inability to feel pain and the absence of sweat glands. Additionally, aberrant TrkA signaling has been implicated in various cancers, where it can act as an oncogene.

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