biology

Tropomyosin receptor kinase B

Tropomyosin receptor kinase B is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Tropomyosin receptor kinase B rather than just read about it. In short: Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF).

Key takeaways

Tropomyosin receptor kinase B belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Tropomyosin receptor kinase B to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Tropomyosin receptor kinase B from memory before moving on to harder problems.

Reference excerpt

Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF).

Function Tropomyosin receptor kinase B is the high-affinity catalytic receptor for several "neurotrophins", small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3). As such, TrkB mediates the multiple effects of these neurotrophic factors, which include neuronal differentiation and survival. The TrkB receptor is part of the large family of receptor tyrosine kinases. A tyrosine kinase is an enzyme capable of adding a phosphate group to certain tyrosines on target proteins or substrates. A receptor tyrosine kinase is a tyrosine kinase located at the cellular membrane, and is activated by the binding of a ligand to the receptor's extracellular domain. Other examples of tyrosine kinase receptors include the insulin receptor, the IGF1 receptor, the MuSK protein receptor, the Vascular Endothelial Growth Factor (or VEGF) receptor, etc.

Currently, there are three TrkB isoforms in the mammalian CNS. The full-length isoform (TK+) is a typical tyrosine kinase receptor and transduces the BDNF signal via Ras-ERK, PI3K, and PLCγ. In contrast, two truncated isoforms (TK-: T1 and T2) possess the same extracellular domain, transmembrane domain, and first 12 intracellular amino acid sequences as TK+. However, the C-terminal sequences are isoform-specific (11 and 9 amino acids, respectively). BDNF binding initiates TrkB dimerization and trans-autophosphorylation, revealing binding sites for PLCγ and Shc proteins. When PLCγ binds to TrkB, PIP2 is hydrolyzed into IP3 and DAG. IP3 binds to the endoplasmic reticulum, inducing calcium release, while DAG stimulates Protein Kinase C (PKC). PKC activation is implicated in neuronal plasticity and survival, among other effects. Shc binding recruits PI3K, which promotes AKT and MAPK/ERK signaling cascades involved in dendritogenesis, cellular differentiation, and proliferation. TrkB.T1 isoforms prevent autophosphorylation, limiting full-length TrkB signaling and its associated effects on neuronal plasticity. However, TrkB.T1 has separate signaling pathways in astrocytes and glial cells, regulating calcium influx and cell morphology. Disease states associated with overexpression of TrkB.T1 include ischemia, stroke, spinal cord injury, neurodegenerative disorders, and chronic pain.

Family members

TrkB is part of a sub-family of protein kinases which includes also TrkA and TrkC. There are other neurotrophic factors structurally related to BDNF: NGF (for nerve growth factor), NT-3 (for neurotrophin-3) and NT-4 (for neurotrophin-4). While TrkB mediates the effects of BDNF, NT-4 and NT-3, TrkA is bound and thereby activated only by NGF. Further, TrkC binds and is activated by NT-3. TrkB binds BDNF and NT-4 more strongly than it binds NT-3. NT-3 has a greater binding affinity for TrkC than TrkB.

Clinical Implications

Cancer Although originally identified as an oncogenic fusion in 1982, only recently has there been a renewed interest in the Trk family as it relates to its role in human cancers because of the identification of NTRK1 (TrkA), NTRK2 (TrkB) and NTRK3 (TrkC) gene fusions and other oncogenic alterations in a number of tumor types. A number of Trk inhibitors are (in 2015) in clinical trials and have shown early promise in shrinking human tumors.

Neurodegenerative Diseases TrkB and its ligand BDNF have been associated to both normal brain function and in the pathology and progression of Alzheimer's disease (AD) and other neurodegenerative disorders. First of all, BDNF/TrkB signalling has been implicated in long-term memory formation, the regulation of long-term potentiation, as well as hippocampal synaptic plasticity. In particular, neuronal activity has been shown to lead to an increase in TrkB mRNA transcription, as well as changes in TrkB protein trafficking, including receptor endocytosis or translocation. Both TrkB and BDNF are downregulated in the brain of early AD patients with mild cognitive impairments, while work in mice has shown that reducing TrkB levels in the brain of AD mouse models leads to a significant increase in memory deficits. In addition, combining the induction of adult hippocampal neurogenesis and increasing BDNF levels lead to an improved cognition, mimicking exercise benefits in AD mouse models. The effect of TrkB/BDNF signalling on AD pathology has been shown to be in part mediated by an increase in δ-secretase levels, via an upregulation of the JAK2/STAT3 pathway and C/EBPβ downstream of TrkB. Additionally, TrkB has been shown to reduce amyloid-β production by APP binding and phosphorylation, while TrkB cleavage by δ-secretase blocks normal TrkB activity. Dysregulation of the TrkB/BDNF pathway has been implicated in other neurological and neurodegenerative conditions, including stroke, Huntington's Disease, Parkinson's Disease, Amyotrophic lateral sclerosis and stress-related disorders.

Epilepsy TrkB activation is implicated in KCC2 downregulation in the CNS. KCC2 cotransports potassium and chloride ions out of the cell. Chloride levels inside the cell remain low, so when GABAA receptors are activated, extracellular chloride can flow into the cell, inducing hyperpolarization. KCC2 downregulation causes intracellular Cl- accumulation, decreasing the electrochemical gradient that is critical for inhibitory GABAA signaling. Altered inhibitory transmission caused by KCC2 downregulation is one mechanism implicated in epilepsy.

Depression In the early 2020s, it was reported that some antidepressants, ketamine, and certain psychedelic drugs including LSD and psilocin interacted directly with TrkB and that this action might be involved in their antidepressant effects. However, subsequent studies with LSD and psilocin failed to reproduce these findings and instead found no interaction of these agents with TrkB.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Tropomyosin receptor kinase B

Start with the simplest possible case. Write down what Tropomyosin receptor kinase B claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Tropomyosin receptor kinase B before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Tropomyosin receptor kinase B ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Tropomyosin receptor kinase B

In research: Tropomyosin receptor kinase B appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Tropomyosin receptor kinase B in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Tropomyosin receptor kinase B is common in secondary-school and first-year university syllabi. It links to neighbouring topics Developmental neuroscience, Genes on human chromosome 9, Tyrosine kinase receptors, so understanding it makes those chapters shorter.
In everyday life: Look for Tropomyosin receptor kinase B outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Ask Teacher Smith questions about this articleOpens your AI tutor with a question about “Tropomyosin receptor kinase B” →

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Tropomyosin receptor kinase B in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Tropomyosin receptor kinase B means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Tropomyosin receptor kinase B out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Tropomyosin receptor kinase B in simple terms?

Why does Tropomyosin receptor kinase B matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Tropomyosin receptor kinase B?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Tropomyosin receptor kinase B.