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An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons.

Riccio, A; Pierchala, BA; Ciarallo, CL; Ginty, DD; (1997) An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science , 277 (5329) pp. 1097-1100.

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Abstract

Nerve growth factor (NGF) is a neurotrophic factor secreted by cells that are the targets of innervation of sympathetic and some sensory neurons. However, the mechanism by which the NGF signal is propagated from the axon terminal to the cell body, which can be more than 1 meter away, to influence biochemical events critical for growth and survival of neurons has remained unclear. An NGF-mediated signal transmitted from the terminals and distal axons of cultured rat sympathetic neurons to their nuclei regulated phosphorylation of the transcription factor CREB (cyclic adenosine monophosphate response element-binding protein). Internalization of NGF and its receptor tyrosine kinase TrkA, and their transport to the cell body, were required for transmission of this signal. The tyrosine kinase activity of TrkA was required to maintain it in an autophosphorylated state upon its arrival in the cell body and for propagation of the signal to CREB within neuronal nuclei. Thus, an NGF-TrkA complex is a messenger that delivers the NGF signal from axon terminals to cell bodies of sympathetic neurons.

Type: Article
Title: An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons.
Location: United States
Keywords: Animals, Animals, Newborn, Axonal Transport, Axons, Carbazoles, Cell Membrane, Cells, Cultured, Cyclic AMP Response Element-Binding Protein, Indole Alkaloids, Microspheres, Nerve Growth Factors, Neurons, Phosphorylation, Proto-Oncogene Proteins, Rats, Receptor Protein-Tyrosine Kinases, Receptor, trkA, Receptors, Nerve Growth Factor, Signal Transduction, Superior Cervical Ganglion
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/82136
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