Name: trk receptors in cell signaling
Uploaded: 2026-08-26T08:19:41.990Z
Duration: 1 min 13 s
Channel: JoVE

Enzyme-linked receptors are transmembrane proteins that act as both receptors and enzymes, catalyzing intracellular reactions.One major family of enzyme-linked receptors is receptor tyrosine kinases, or RTKs.When a signaling molecule, called a ligand, binds to the extracellular domain of RTKs, two receptor molecules dimerize, or join together, within the membrane.Dimerization activates the tyrosine kinase domains on the cytoplasmic tails of the receptors.Each RTK in the dimer transfers phosphate groups from ATP to specific tyrosine residues on the opposing receptor. This process is called trans-autophosphorylation.The phosphorylated tyrosines act as docking sites for intracellular relay proteins. These proteins bind to specific phosphotyrosines, become activated, and start downstream signal transduction pathways that produce diverse cellular responses.

enzyme-linked receptors

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5, while TrkC is specific for neurotrophin-3.The Trk receptors have a single transmembrane domain, with a growth factor binding site on the extracellular portion and an enzyme activation site intracellularly. Trk receptors can be monomeric or dimerized, where two Trk receptors are linked. Either a single growth factor binds two monomeric receptors causing them to dimerize, or the growth factor binds both sites on a pre-dimerized receptor to activate the receptor.Once the receptors are bound, the activated tyrosine kinases cross-phosphorylate the tyrosines using phosphate from ATP and donating them to each other. Phosphorylated tyrosines are recognized as docking sites by intracellular signaling protein domains, such as the Src homology 2 (SH2). Each docking site is used by different signaling proteins, which increases the variety of downstream effects regulated by these receptors.The interaction between NGF and TrkA has garnered attention for its role in the progression of Alzheimer&#x27;s disease, a disorder in which neurons develop amyloid plaques. Amyloid-beta is a cytotoxic fragment of the amyloid precursor protein (APP). It is hypothesized that binding NGF to the TrkA receptor decreases the generation of amyloid-beta by joining APP to the TrkA receptor. This eliminates the ability of beta-secretase 1 (BACE1) to cleave APP into amyloid-beta. Furthermore, the TrkA receptor can shuttle APP to the Golgi, where BACE1 enzymes are rare. In the brain of Alzheimer&#x27;s patients, there is a decreased generation of TrkA/APP complex in areas critical to learning and memory, like the hippocampus.

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors ...

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Cell Signaling

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trk receptors in cell signaling

Trk receptors are enzyme-linked receptors that help cells respond to growth factors and some hormones. They belong to the receptor tyrosine kinase, or RTK, family. These receptors can trigger several signals inside a cell after they are activated.

Neurotrophin receptors are one RTK group and include TrkA, TrkB, and TrkC, which are tropomyosin-related kinase receptors. TrkA binds nerve growth factor, neurotrophin-6, and neurotrophin-7. TrkB binds brain-derived neurotrophic factor, or BDNF, and neurotrophin-4/5. TrkC is specific for neurotrophin-3.

Each Trk receptor has one transmembrane segment. The growth factor binding site is outside the cell, while the enzyme activation site is inside the cell. Trk receptors can exist as single receptors or as dimers, meaning two receptors linked together. A growth factor can bind two separate receptors and cause dimerization, or it can bind both sites on a receptor pair that is already dimerized.

After binding, the activated tyrosine kinases cross-phosphorylate each other. This means they transfer phosphate from ATP to tyrosine amino acids on the partner receptor. The phosphorylated tyrosines then act as docking sites for signaling proteins inside the cell. Some of these proteins use Src homology 2, or SH2, domains to bind.

Different docking sites recruit different signaling proteins, so these receptors can produce a wide range of downstream effects. The NGF-TrkA interaction is also important in Alzheimer's disease. In this disorder, neurons develop amyloid plaques. Amyloid-beta is a toxic fragment made from amyloid precursor protein, or APP.

Binding NGF to TrkA is thought to reduce amyloid-beta production by bringing APP together with the TrkA receptor. This can block beta-secretase 1, or BACE1, from cutting APP into amyloid-beta. TrkA can also move APP to the Golgi, where BACE1 is rare. In brains from patients with Alzheimer's disease, less TrkA/APP complex is made in areas such as the hippocampus, which is important for learning and memory.

Trk Receptors in Cell Signaling

what is cell signaling?

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paracrine signaling

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Trk receptors are enzyme-linked receptors that help cells respond to growth factors and some hormones. They belong to the receptor tyrosine kinase, or RTK, family. These receptors can trigger several signals inside a cell after they are activated. Neurotrophin receptors are one RTK group and include TrkA, TrkB, and TrkC, which are tropomyosin-related kinase receptors. TrkA binds nerve growth factor, neurotrophin-6, and neurotrophin-7. TrkB binds brain-derived neurotrophic factor, or BDNF, and...

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what are second messengers?

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intracellular signaling cascades

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Cell-surface receptor signal cascades move information from outside the cell into the cytoplasm. This process is called signal transduction. It happens only with cell-surface receptors, because they cannot interact with most cell parts, such as DNA. Internal receptors are different. They can interact directly with DNA in the nucleus and help start protein synthesis. When a ligand binds to a receptor, the receptor changes shape. That shape change affects the receptor’s intracellular domain or...

key terms and concepts

Explore how TrkA, TrkB, and TrkC receptor tyrosine kinases work, how they dimerize and signal, and why NGF-TrkA matters in Alzheimer's disease.

Trk Receptors in Cell Signaling | JoVE K12

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Trk Receptors in Cell Signaling

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