Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells

@article{Ip1993SimilaritiesAD,
  title={Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells},
  author={Nancy Y. Ip and Trevor Stitt and Peter M. Tapley and R{\"u}diger Klein and David J. Glass and James P. Fandl and Lloyd A Greene and Mariano Barbacid and George D. Yancopoulos},
  journal={Neuron},
  year={1993},
  volume={10},
  pages={137-149}
}
We have exploited a battery of approaches to address several controversies that have accompanied the expansion of the nerve growth factor (NGF) family of neurotrophic factors and the identification of the Trk tyrosine kinases as receptors for these factors. For example, we find that a recently cloned mammalian neurotrophin, known as either neurotrophin-4 or neurotrophin-5 and assigned widely differing receptor specificities, represents the functional counterpart of Xenopus neurotrophin-4 and is… Expand
The Trk family of neurotrophin receptors.
  • M. Barbacid
  • Biology, Medicine
  • Journal of neurobiology
  • 1994
TLDR
Preliminary characterization of these mutant mice has provided significant information regarding the role of these receptors in the ontogeny of the mammalian nervous system, and TrkC-deficient mice display strikingly abnormal movements consistent with loss of proprioception. Expand
Structural determinants of Trk receptor specificities using BNDF‐based neurotrophin chimeras
TLDR
It is revealed that, although BDNF is absolutely conserved in mammals, substitution of several small variable regions from NGF into the BDNF backbone did not lead to significant loss in TrkB activity or gain in TrkA activity. Expand
Structural and Functional Properties of the TRK Family of Neurotrophin Receptors
  • M. Barbacid
  • Biology, Medicine
  • Annals of the New York Academy of Sciences
  • 1995
TLDR
Characterization of mutant mice lacking each of these tyrosine-kinase receptors by gene targeting in embryonic stem cells is providing relevant information regarding the critical role that these receptors play in the ontogeny of the mammalian nervous system. Expand
Requirement for Neurotrophin-3 in the Development of the Muscle Proprioceptive System
TLDR
A physiological role for NT-3 during development of the nervous system is confirmed and consistent with previous results from culture studies and manipulations of the embryo and it modulates ligand interactions with the high-affinity receptor. Expand
Binding of Neurotrophin-3 to p75, TrkA, and TrkB Mediated by a Single Functional Epitope Distinct from That Recognized by TrkC (*)
TLDR
The mutant NT-3 described here may be of greater advantage than nativeNT-3 when a trophic activity needs to be specifically targeted to TrkC-expressing neurons and provides a monospecific neurotrophin for future therapeutic development. Expand
The neurotrophins and their receptors.
TLDR
The neurotrophins, which include nerve growth factor (NGF) and its relatives, were discovered and characterized for their distinctive ability to promote survival and differentiation of postmitotic neurons and have recently been found to utilize a family of receptor tyrosine kinases similar to those used by normally mitogenic growth factors. Expand
Receptors and Signaling Pathways Used by the Neurotrophins, CNTF and a New Family of Neurotrophic Factors, the EFLs
TLDR
This chapter presents a schematic representation of neurotrophin receptor activation and the receptor system used by ciliary neurotrophic factor and implications for other cytokine receptor systems. Expand
Immunocytochemical localization of TrkB in the central nervous system of the adult rat
TLDR
The detection of TrkB immunoreactivity on cell bodies and dendrites is consistent with recent models suggesting that neurotrophins may be derived from presynaptic and/or autocrine sources in addition to the classical postsynaptic target. Expand
The binding epitopes of neurotrophin‐3 to its receptors trkC and gp75 and the design of a multifunctional human neurotrophin.
TLDR
The results suggest that the specificity among neurotrophic factors is not solely encoded in sequence diversity, but rather in the way each neurotrophin interacts with its preferred receptor. Expand
Characterization of Neurotrophin and Trk Receptor Functions in Developing Sensory Ganglia Direct NT-3 Activation of TrkB Neurons In Vivo
TLDR
It is shown that, during the major period of neurogenesis, NT-3 is required to maintain neurons that express TrkB in addition to those thatexpress TrkC but is not essential for neurons expressing TrkA, and that survival of cells expressing both receptors can be maintained by activation of either one alone. Expand
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References

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trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor
TLDR
It is demonstrated that all three of these neuronal survival molecules bind similarly to the low affinity NGF receptor, but that BDNF and NT-3, unlike NGF, do not act via the high affinity N GF receptor. Expand
Neurotrophin-5: A novel neurotrophic factor that activates trk and trkB
TLDR
NT-5 is structurally related to nerve growth factor and is expressed in embryonic as well as adult tissues and promotes the survival of peripheral sensory and sympathetic neurons and induces differentiation of the pheochromocytoma cell line PC12. Expand
trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3
TLDR
Results indicate that gp145trkC may play an important role in mediating the neurotrophic effects of NT-3, a new member of the trk family of tyrosine protein kinase genes. Expand
The changing scene of neurotrophic factors
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TLDR
The physiological and pathophysiological functions of neurotrophins and CNTF are discussed in the context of their potential use for the treatment of traumatic and degenerative diseases of the peripheral and central nervous systems. Expand
Trkl3 mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor
TLDR
It is demonstrated that TrkB mediates survival and proliferation in response to both BDNF and NT-3 when expressed in a particular strain of NIH 3T3 fibroblasts, with BDNF the more potent ligand. Expand
The trkB tyrosine protein kinase is a receptor for neurotrophin-4
TLDR
XNT-4 and BDNF may interact with at least partially distinct domains within the gp145trkB receptor, a murine tyrosine protein kinase previously identified as a primary receptor for the related brain-derived neurotrophic factor (BDNF). Expand
The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3
TLDR
It is shown that NGF is a powerful mitogen that can induce resting NIH 3T3 cells to enter S phase, grow in semisolid medium, and become morphologically transformed, but this effect is absolutely dependent on expression of gp140trk receptors, but do not require the presence of the previously described low affinity NGF receptor. Expand
The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor
TLDR
Analysis of the trkB gene product, gp145trkB, in NIH 3T3 cells indicates that this tyrosine kinase receptor is rapidly phosphorylated on tyosine residues upon exposure to the NGF-related neurotrophic factors BDNF and NT-3. Expand
Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family
TLDR
Taking advantage of sequence identities between NGF and BDNF, a third member of this family of secretory proteins is identified, which is named neurotrophin-3, and a remarkable number of amino acid identities are revealed, including all cys-teine residues. Expand
The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3
TLDR
It is shown that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on tyrosine of gp 145trkB, one of the receptors encoded by trkB, indicating that gp145trkB may function as a neurotrophic receptor for BDNF andNT-3. Expand
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