Identification and Characterization of Novel Substrates of Trk Receptors in Developing Neurons

@article{Qian1998IdentificationAC,
  title={Identification and Characterization of Novel Substrates of Trk Receptors in Developing Neurons},
  author={X. Qian and A. Riccio and Y. Zhang and D. Ginty},
  journal={Neuron},
  year={1998},
  volume={21},
  pages={1017-1029}
}
Neurotrophins influence growth and survival of specific populations of neurons through activation of Trks, members of the receptor tyrosine kinase (RTK) family. In this report, we describe the identification and characterization of two substrates of Trk kinases, rAPS and SH2-B, which are closely related Src homolog 2 (SH2) domain-containing signaling molecules. rAPS and SH2-B are substrates of TrkB and TrkC in cortical neurons and SH2-B is a substrate of TrkA in sympathetic neurons. Moreover… Expand
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References

SHOWING 1-10 OF 69 REFERENCES
Neurotrophin signal transduction by the Trk receptor.
TLDR
The attempts to understand the mechanisms used by Trk to generate the many phenotypic responses of PC12 cells to NGF are summarized. Expand
Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF
TLDR
Tyrosine phosphorylation of trk by NGF is rapid, specific and occurs with picomolar quantities of factor, indicating that the response is mediated by physiological amounts of NGF. Expand
Trk receptors use redundant signal transduction pathways involving SHC and PLC-γ1 to mediate NGF responses
TLDR
A model whereby Trk receptors utilize at least partially redundant signal transduction pathways to mediate NGF responses is suggested, whereby TrK receptors can activate Erk1 by either SHC- or PLC-gamma 1-dependent signaling pathways. Expand
Involvement of ras p21 in neurotrophin-induced response of sensory, but not sympathetic neurons
TLDR
Results indicate an involvement of ras p21 in the signal transduction of neurotrophic factors in sensory, but not sympathetic or ciliary neurons, pointing to the existence of different signaling pathways not only in CNTF-responsive, but also in neurotrophin-responsive neuronal populations. Expand
Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation
TLDR
Results indicate that APS, SH2-B and Lnk form a new adaptor family that links immune receptors to signaling pathways involved in tyrosine-phosphorylation, and plays a role in linkage from BCR to Shc/Grb2 pathway. Expand
The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling
TLDR
Results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling. Expand
Differential Regulation of p21ras Activation in Neurons by Nerve Growth Factor and Brain-derived Neurotrophic Factor (*)
TLDR
Results indicate that in neurons, the pathways activated by NGF and BDNF are differentially regulated and that prolonged exposure to BDNF results in the inability of TrkB to bind its ligand. Expand
The trk proto-oncogene encodes a receptor for nerve growth factor
TLDR
The results indicate that gp140trk is a functional NGF receptor that mediates at least some of the signal transduction processes initiated by this neurotrophic factor. Expand
Early events in neurotrophin signalling via Trk and p75 receptors
TLDR
Although many findings point to clear involvement for p75 in neurotrophin signalling, the molecular mechanisms by which these occur are just beginning to be identified. Expand
ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK
p21c-ras plays a critical role in mediating tyrosine kinase-stimulated cell growth and differentiation. However, the pathways through which p21c-ras propagates these signals remain unknown. We reportExpand
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