Nerve growth factor receptor
Encyclopedia
Nerve growth factor receptors are a group of growth factor receptor
s which specifically bind to neurotrophin
s.
There are two classes of receptors, p75 and the "Trk" family of Tyrosine kinase
s receptors.
is a receptor tyrosine kinase
(meaning it mediates its actions by causing the addition of phosphate
molecules on certain tyrosines in the cell, activating cellular signaling).
There are other related Trk receptors (TrkB
and TrkC
), and there are other neurotrophic factors structurally related to NGF (BDNF, NT-3, and NT-4
)
, commonly known as "p75", plays a less clear role.
LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin.
However, although NGF has been classically described as promoting neuron survival and differentiation, research performed in the early 2000s suggest that NGF with its prodomain attached (proNGF) can elicit apoptosis of cells that are positive for the LNGFR and negative for TrkA
.
Secreted proNGF has been demonstrated in a variety of neuronal and non-neuronal cell populations. It has been proposed that secreted proNGF can elicit neuron
death in a variety of neurodegenerative conditions, including Alzheimer's disease
, following the observation of an increase of proNGF in the nucleus
basalis of postmortem Alzheimer's brains.
Growth factor receptor
A growth factor receptor is a receptor which binds to growth factor.These receptors may use the JAK/STAT, MAP kinase, and PI3 kinase pathways....
s which specifically bind to neurotrophin
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...
s.
There are two classes of receptors, p75 and the "Trk" family of Tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
s receptors.
- p75 is a low affinity neurotrophin receptor, to which all neurotrophins bind. It is a member of the tumour necrosis super family. In some contexts, the phrase "x" only applies to this receptor.
- The Trk familyTrk receptorTrk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signal cascades...
include TrkATrkAHigh affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
, TrkBTrkBTrkB receptor also known as TrkB tyrosine kinase 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.-Function:...
, and TrkCTrkCNT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
, and will only bind with specific neurotrophins, but with a much higher affinity. The Trks mediate the functional signals of the neurotrophins. - NGF binds to TrkA, BDNF and NT-4 bind to TrkB and NT-3 binds to TrkCTrkCNT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
. In addition NT-3 also binds to and activates TrkA and TrkB but it does so less efficiently. - Whilst the Trk receptors have a clearly defined trophic role, p75 receptors activate signalling pathways which can also result in apoptosisApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
TrkA, B, and C receptors
TrkATrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
is a receptor tyrosine kinase
Receptor tyrosine kinase
Receptor tyrosine kinases s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins....
(meaning it mediates its actions by causing the addition of phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
molecules on certain tyrosines in the cell, activating cellular signaling).
There are other related Trk receptors (TrkB
TrkB
TrkB receptor also known as TrkB tyrosine kinase 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.-Function:...
and TrkC
TrkC
NT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
), and there are other neurotrophic factors structurally related to NGF (BDNF, NT-3, and NT-4
NT-4
Neurotrophin-4 , also known as neurotrophin-5 , is a protein that in humans is encoded by the NTF4 gene.NT-4 is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase....
)
- TrkATrkAHigh affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
mediates the effects of NGF - TrkBTrkBTrkB receptor also known as TrkB tyrosine kinase 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.-Function:...
binds and is activated by BDNF, NT-4NT-4Neurotrophin-4 , also known as neurotrophin-5 , is a protein that in humans is encoded by the NTF4 gene.NT-4 is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase....
, and NT-3 - TrkCTrkCNT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
binds and is activated only by NT-3
LNGFR receptor
The other NGF receptor, the LNGFR, (for Low affinity nerve growth factor receptorLow Affinity Nerve Growth Factor Receptor
The Low-Affinity Nerve Growth Factor Receptor is one of the two receptor types for the neurotrophins, a family of protein growth factors that stimulate neuronal cells to survive and differentiate...
, commonly known as "p75", plays a less clear role.
LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin.
However, although NGF has been classically described as promoting neuron survival and differentiation, research performed in the early 2000s suggest that NGF with its prodomain attached (proNGF) can elicit apoptosis of cells that are positive for the LNGFR and negative for TrkA
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
.
Secreted proNGF has been demonstrated in a variety of neuronal and non-neuronal cell populations. It has been proposed that secreted proNGF can elicit neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
death in a variety of neurodegenerative conditions, including Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, following the observation of an increase of proNGF in the nucleus
Nucleus (neuroanatomy)
In neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
basalis of postmortem Alzheimer's brains.