Difference between revisions of "Low-affinity nerve growth factor receptor"
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| Nerve growth factor receptor (TNFR superfamily, member 16) | |||||||||||||
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| 250px PDB rendering based on 1sg1. | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | NGFR; CD271; TNFRSF16; p75(NTR) | ||||||||||||
| External IDs | OMIM: 162010 MGI: 97323 HomoloGene: 1877 GeneCards: NGFR Gene | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| More reference expression data | |||||||||||||
| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 4804 | 18053 | |||||||||||
| Ensembl | ENSG00000064300 | ENSMUSG00000000120 | |||||||||||
| UniProt | P08138 | Q8BYY1 | |||||||||||
| RefSeq (mRNA) | NM_002507 | NM_033217 | |||||||||||
| RefSeq (protein) | NP_002498 | NP_150086 | |||||||||||
| Location (UCSC) | Chr 17: 44.93 - 44.95 Mb | Chr 11: 95.38 - 95.4 Mb | |||||||||||
| PubMed search | [1] | [2] | |||||||||||
The Low-Affinity Nerve Growth Factor Receptor (also called the LNGFR or p75 neurotrophin 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. The precise function of the LNGFR is somewhat controversial, in contrast to the function of the high-affinity receptor family for the neurotrophins, the Trk receptor tyrosine kinases such as TrkA.
Contents
The Neurotrophins
The neurotrophins are composed of four proteins, all of which bind to the LNGFR: Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4).
Nerve growth factor, the prototypical growth factor, is a protein secreted by a neuron's target. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high-affinity receptor (TrkA), and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.
The activation of TrkA by NGF is critical in inducing the survival and differentiation caused by this growth factor.
However, NGF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkA (pronounced "Track A") and the LNGFR.
The Trk family of receptor tyrosine kinases
TrkA 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. Also, there are other neurotrophic factors structurally related to NGF: BDNF (for Brain-Derived Neurotrophic Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkA mediates the effects of NGF, TrkB binds and is activated by BDNF, NT-4, and NT-3, and TrkC binds and is activated only by NT-3.
The role of the LNGFR
As opposed to TrkA, the LNGFR plays a somewhat less clear role in NGF biology. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. Cells that express both the LNGFR and the Trk receptors might, therefore, have a greater activity, since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that, in the absence of a co-expressed TrkA, the LNGFR may signal a cell to die via apoptosis; so, therefore, cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.[1]
Recent research has suggested a number of roles for the LNGFR, including in development of the eyes and sensory neurons,[2][3] and in repair of muscle and nerve damage in adults.[4][5][6]
Interactions
Low-affinity nerve growth factor receptor has been shown to interact with PRKACB,[7] FSCN1,[8] TRAF4,[9][10] Nerve growth factor,[11][12] TRAF2,[9] NDN,[13][14][15] NGFRAP1[16] and MAGEH1.[15]
References
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<references />, or <references group="..." />Further reading
- Buxser S, Puma P, Johnson G (10 February 1985). "Properties of the nerve growth factor receptor. Relationship between receptor structure and affinity". Journal of Biological Chemistry. 260 (3): 1917–26. PMID 2981877.
- Glass D, Nye S, Hantzopoulos P, Macchi M, Squinto S, Goldfarb M, Yancopoulos G (1991). "TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor". Cell. 66 (2): 405–13. doi:10.1016/0092-8674(91)90629-D. PMID 1649703.
- Ibáñez C (2002). "Jekyll-Hyde neurotrophins: the story of proNGF". Trends in Neurosciences. 25 (6): 284–6. doi:10.1016/S0166-2236(02)02169-0. PMID 12086739.
- Radeke M, Misko T, Hsu C, Herzenberg L, Shooter E (1987). "Gene transfer and molecular cloning of the rat nerve growth factor receptor". Nature. 325 (6105): 593–597. doi:10.1038/325593a0. PMID 3027580.
External links
ru:NGFR- ↑ Citation: Ibáñez, 2002
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