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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/9430

Title: Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses
Authors: Stephens, RM
Loeb, DM
Copeland, TD
Pawson, Tony
Greene, LA
Kaplan, DR
Keywords: Nerve Growth Factors
Phospholipase C
Receptor Protein-Tyrosine Kinases
Signal Transduction
Issue Date: Mar-1994
Publisher: Cell Press
Citation: Neuron. 1994 Mar;12(3):691-705.
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.
URI: http://www.neuron.org/
ISSN: 0896-6273
Appears in Collections:Pawson, Tony
Pawson, Tony

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