Tropomyosin receptor kinase A: Difference between revisions

Revision as of 15:44, 9 February 2025

A receptor tyrosine kinase involved in the development and function of the nervous system

Tropomyosin receptor kinase A (TrkA), also known as NTRK1, is a receptor tyrosine kinase that is encoded by the NTRK1 gene in humans. It is a member of the neurotrophic tyrosine kinase receptor family and plays a crucial role in the development and function of the nervous system.

Structure

TrkA is a transmembrane protein that consists of 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 activated by binding to NGF, which leads to receptor dimerization and autophosphorylation of specific 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 growth.

Role in Disease

Mutations in the NTRK1 gene can lead to a variety of disorders. For example, loss-of-function mutations are associated with congenital insensitivity to pain with anhidrosis (CIPA), a rare genetic disorder characterized by the inability to feel pain and the absence of sweat glands. On the other hand, gain-of-function mutations or gene fusions involving NTRK1 can result in oncogenic activation, contributing to the development of certain cancers.

Clinical Significance

TrkA is a target for cancer therapies, particularly in tumors that harbor NTRK1 gene fusions. Inhibitors of TrkA, such as larotrectinib and entrectinib, have been developed and approved for the treatment of cancers with these genetic alterations. These therapies have shown efficacy in reducing tumor size and improving patient outcomes.

Research

Ongoing research is focused on understanding the precise mechanisms of TrkA signaling and its role in various physiological and pathological processes. Studies are also exploring the potential of TrkA as a therapeutic target in neurodegenerative diseases and other conditions.

Related pages

References

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-'''Tropomyosin receptor kinase A''' ('''TrkA'''), also known as '''nerve growth factor receptor''' (NGFR), is a protein that in humans is encoded by the ''NTRK1'' gene. TrkA is a member of the tropomyosin-related kinase (Trk) family of tyrosine kinase receptors, which are key regulators in the development and maintenance of the nervous system. TrkA specifically binds to and is activated by nerve growth factor (NGF), leading to cellular differentiation and survival signals, particularly in neural cells.
+{{Short description|A receptor tyrosine kinase involved in the development and function of the nervous system}}
+{{Use dmy dates|date=October 2023}}
-== Function ==
+'''Tropomyosin receptor kinase A''' ('''TrkA'''), also known as '''NTRK1''', is a [[receptor tyrosine kinase]] that is encoded by the ''NTRK1'' gene in humans. It is a member of the [[neurotrophic tyrosine kinase receptor]] family and plays a crucial role in the development and function of the [[nervous system]].
-TrkA plays a critical role in the development and function of the nervous system. Upon binding with its ligand, NGF, TrkA undergoes dimerization and autophosphorylation, which activates its kinase activity. This activation leads to the phosphorylation of downstream signaling molecules involved in the PI3K/AKT and MAPK/ERK pathways, which are crucial for cell survival, differentiation, and growth. TrkA signaling is essential for the survival and maintenance of sympathetic and sensory neurons during development and in adult organisms.
-== Clinical Significance ==
+==Structure==
-Alterations in TrkA signaling have been implicated in a variety of human diseases. Overexpression or mutation of the ''NTRK1'' gene can lead to the development of cancers, including certain types of thyroid cancer and neuroblastoma. Conversely, reduced expression or activity of TrkA has been associated with increased susceptibility to neurodegenerative diseases, such as Alzheimer's disease, due to the loss of trophic support for neurons.
+TrkA is a transmembrane protein that consists of 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.
-In addition to its role in disease, TrkA is a potential therapeutic target. Agonists of TrkA are being explored for their potential to promote neuronal survival and regeneration, which could be beneficial in treating neurodegenerative conditions and nerve injury. Conversely, TrkA antagonists and kinase inhibitors are being investigated for their potential in cancer therapy, to inhibit the growth of tumors that rely on TrkA signaling for survival and proliferation.
+==Function==
+TrkA is primarily activated by binding to NGF, which leads to receptor dimerization and autophosphorylation of specific 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 growth.
-== Genetics ==
+==Role in Disease==
-The ''NTRK1'' gene, located on chromosome 1q21-q22, encodes the TrkA protein. Mutations in this gene can lead to congenital insensitivity to pain with anhidrosis (CIPA), a rare genetic disorder characterized by the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition highlights the importance of TrkA in the development and function of the sensory and sympathetic nervous systems.
+Mutations in the ''NTRK1'' gene can lead to a variety of disorders. For example, loss-of-function mutations are associated with [[congenital insensitivity to pain with anhidrosis]] (CIPA), a rare genetic disorder characterized by the inability to feel pain and the absence of sweat glands. On the other hand, gain-of-function mutations or gene fusions involving ''NTRK1'' can result in oncogenic activation, contributing to the development of certain cancers.
-== See Also ==
+==Clinical Significance==
-* [[Nerve Growth Factor]]
+TrkA is a target for cancer therapies, particularly in tumors that harbor ''NTRK1'' gene fusions. Inhibitors of TrkA, such as [[larotrectinib]] and [[entrectinib]], have been developed and approved for the treatment of cancers with these genetic alterations. These therapies have shown efficacy in reducing tumor size and improving patient outcomes.
-* [[Tropomyosin receptor kinase B]]
-* [[Tropomyosin receptor kinase C]]
+==Research==
+Ongoing research is focused on understanding the precise mechanisms of TrkA signaling and its role in various physiological and pathological processes. Studies are also exploring the potential of TrkA as a therapeutic target in neurodegenerative diseases and other conditions.
+==Related pages==
+* [[Nerve growth factor]]
+* [[Receptor tyrosine kinase]]
 * [[Neurotrophin]]
-* [[Tyrosine kinase receptor]]
-== References ==
-<references />
+==References==
+{{Reflist}}
-[[Category:Signal transduction]]
+[[Category:Receptor tyrosine kinases]]
-[[Category:Tyrosine kinase receptors]]
+[[Category:Neurotrophin receptors]]
-[[Category:Neuroscience]]
+[[Category:Oncogenes]]
-{{Medicine-stub}}
+[[File:Wikipedia trka.png|thumb|right|Diagram of the TrkA receptor structure and signaling pathways.]]