Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses - PubMed (original) (raw)
Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses
R M Stephens et al. Neuron. 1994 Mar.
Free article
Abstract
In response to NGF, the Trk receptor tyrosine kinase forms a complex with SHC, a protein that couples receptor tyrosine kinases to p21ras. Complex formation between Trk and SHC, SHC tyrosine phosphorylation, and association of SHC with Grb2 were mediated by autophosphorylation at Y490 in Trk [sequence: see text]. To determine the role of SHC and other Trk substrates in NGF signaling, Trk receptors with mutations in Y490 and Y785 (the PLC-gamma 1 association site) were introduced into PC12nnr5 cells. NGF treatment of PC12nnr5 cells expressing Trk with mutations in either substrate-binding site resulted in normal neurite outgrowth and Erk1 activity and tyrosine phosphorylation. However, PC12nnr5 cells expressing Trk with mutations at both sites failed to stably extend neurites and efficiently induce Erk1 activity and tyrosine phosphorylation in response to NGF. We postulate that Trk receptors can activate Erk1 by either SHC- or PLC-gamma 1-dependent signaling pathways. These results suggest a model whereby Trk receptors utilize at least partially redundant signal transduction pathways to mediate NGF responses.
Similar articles
- The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.
Ashcroft M, Stephens RM, Hallberg B, Downward J, Kaplan DR. Ashcroft M, et al. Oncogene. 1999 Aug 12;18(32):4586-97. doi: 10.1038/sj.onc.1202814. Oncogene. 1999. PMID: 10467403 - Autophosphorylation of activation loop tyrosines regulates signaling by the TRK nerve growth factor receptor.
Cunningham ME, Stephens RM, Kaplan DR, Greene LA. Cunningham ME, et al. J Biol Chem. 1997 Apr 18;272(16):10957-67. doi: 10.1074/jbc.272.16.10957. J Biol Chem. 1997. PMID: 9099755 - Neurotrophin signal transduction by the Trk receptor.
Kaplan DR, Stephens RM. Kaplan DR, et al. J Neurobiol. 1994 Nov;25(11):1404-17. doi: 10.1002/neu.480251108. J Neurobiol. 1994. PMID: 7852994 Review. - Trk receptors: roles in neuronal signal transduction.
Huang EJ, Reichardt LF. Huang EJ, et al. Annu Rev Biochem. 2003;72:609-42. doi: 10.1146/annurev.biochem.72.121801.161629. Epub 2003 Mar 27. Annu Rev Biochem. 2003. PMID: 12676795 Review.
Cited by
- Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease.
Forsell P, Parrado Fernández C, Nilsson B, Sandin J, Nordvall G, Segerdahl M. Forsell P, et al. Pharmaceuticals (Basel). 2024 Jul 28;17(8):997. doi: 10.3390/ph17080997. Pharmaceuticals (Basel). 2024. PMID: 39204102 Free PMC article. Review. - Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: Case reports and a review of the literature.
Cho JH, Hwang S, Kwak YH, Yum MS, Seo GH, Koh JY, Ju YS, Yoon JH, Kang M, Do HS, Kim S, Kim GH, Bae H, Lee BH. Cho JH, et al. Mol Genet Genomic Med. 2024 Apr;12(4):e2430. doi: 10.1002/mgg3.2430. Mol Genet Genomic Med. 2024. PMID: 38581121 Free PMC article. Review. - Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex.
Cornejo F, Franchini N, Cortés BI, Elgueta D, Cancino GI. Cornejo F, et al. Front Cell Dev Biol. 2024 Feb 29;12:1357862. doi: 10.3389/fcell.2024.1357862. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 38487272 Free PMC article. - Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.
Lao-Peregrin C, Xiang G, Kim J, Srivastava I, Fall AB, Gerhard DM, Kohtala P, Kim D, Song M, Garcia-Marcos M, Levitz J, Lee FS. Lao-Peregrin C, et al. Cell Rep. 2024 Jan 23;43(1):113595. doi: 10.1016/j.celrep.2023.113595. Epub 2023 Dec 19. Cell Rep. 2024. PMID: 38117654 Free PMC article. - Classification models for predicting the bioactivity of pan-TRK inhibitors and SAR analysis.
Zhao X, Kong Y, Ji Y, Xin X, Chen L, Chen G, Yu C. Zhao X, et al. Mol Divers. 2024 Aug;28(4):2077-2097. doi: 10.1007/s11030-023-10735-2. Epub 2023 Nov 1. Mol Divers. 2024. PMID: 37910346
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous