p75^(LNGFR) regulates Trk signal transduction and NGF-induced neuronal differentiation in MAH cells
We have examined NGF-induced signal transduction events and neuronal differentiation in MAH cells, a neuronal progenitor cell line, in which the expression of the two NGF receptors, p140^(trk) (Trk) and p75^(LNGFR) (p75), has been independently manipulated. Coexpression of a large molar excess of p75 substantially enhances the NGF-induced tyrosine autophosphorylation of Trk, compared with cells expressing Trk alone. MAH cells expressing both Trk and p75 stop dividing and acquire a mature neuronal morphology more rapidly and with greater efficiency than MAH cells expressing Trk alone. These biochemical and biological influences of p75 are not observed using a mutant form of NGF that binds Trk but not p75. These data provide evidence that p75 can modulate signal transduction through Trk in a neuronal progenitor cell context and that such modulation has functional consequences for the neuronal differentiation pathway induced by NGF.
© 1994 by Cell Press. Received 29 December 1993, Revised 26 January 1994, Available online 20 April 2004. We thank George Yancopoulos for communicating his results in advance of publication, Pantelis Tsoulfas and Luis Parada for sending reagents and for helpful discussions, Phil Barker for suggesting the trk primer sequences, Barbara Hempstead for helpful discussions, Steven M. Padilla for technical assistance, and Rochelle Diamond for help with cell sorting. We also thank Kai Zinn and Paul Sternberg for their constructive comments on the manuscript. J. M. V. is supported by an NIH NRSA. M. V. C. was supported by grants from the NIH, the Dorothy Rod bell Cohen Foundation, and a Zenith award from the Alzheimer's Association. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute. This work was supported by a grant from the NIH (NS23476). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.