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Expression of trk in MAH Cells Lacking the p75 Low-Affinty Nerve Growth Factor Receptor is Sufficient to Permit Nerve Growth Factor-Induced Differentiation to Postmitotic Neurons

Verdi, Joseph M. and Ip, Nancy and Yancopolous, George D. and Anderson, David J. (1994) Expression of trk in MAH Cells Lacking the p75 Low-Affinty Nerve Growth Factor Receptor is Sufficient to Permit Nerve Growth Factor-Induced Differentiation to Postmitotic Neurons. Proceedings of the National Academy of Sciences of the United States of America, 91 (9). pp. 3949-3953. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:VERpnas94

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Abstract

We have transfected MAH cells, an immortalized sympathoadrenal progenitor cell line, with a plasmid encoding the 140-kDa Trk protein, a nerve growth factor (NGF) receptor with protein-tyrosine kinase activity. NGF promotes neurite outgrowth and proliferation from such cells, indicating that Trk is sufficient to mediate such responses in the absence of significant levels of the endogenous 75-kDa low-affinity NGF receptor (p75). These initial NGF responses are indistinguishable from those evoked by basic fibroblast growth factor (bFGF). However, NGF is sufficient to promote terminal differentiation of a {approx}8% of trk-transfected MAH cells to postmitotic, NGF-dependent neurons, whereas all cells eventually die in medium with bFGF. Other environmental signals (such as depolarization or ciliary neurotrophic factor) can cooperate with NGF to enhance production of postmitotic NGF-dependent neurons in trk-transfected MAH cells. The terminal differentiation of sympathetic neurons thus involves sequential and cooperative actions of different growth and neurotrophic factors, as well as cell-intrinsic changes in the response to these factors.


Item Type:Article
Additional Information:Copyright © 1994 by National Academy of Sciences Communicated by Norman Davidson, January 12, 1994 We thank Dr. Mariano Barbacid for providing the human trk cDNA clone, Dusty Miller for providing the pLXSHD expression plasmid, Phil Barker and Eric Shooter for providing PCR primers, Steven Padilla for technical assistance, Moses Chao for helpful discussions, and Norman Davidson for constructive comments on an early version of the manuscript. J.M.V. is supported by a National Research Service Award from the National Institutes of Health. D.J.A. is an Associate Investigator of the Howard Hughes Medical Institute. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Record Number:CaltechAUTHORS:VERpnas94
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:VERpnas94
Alternative URL:http://www.pnas.org/cgi/content/abstract/91/9/3949
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ID Code:5334
Collection:CaltechAUTHORS
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Deposited On:10 Oct 2006
Last Modified:14 Nov 2014 19:19

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