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The Journal of Neuroscience, May 1, 1998, 18(9):3273-3281
Competitive Signaling Between TrkA and p75 Nerve Growth Factor
Receptors Determines Cell Survival
Sung Ok
Yoon1,
Patrizia
Casaccia-Bonnefil2,
Bruce
Carter3, and
Moses V.
Chao2
1 Department of Biological Sciences, Columbia
University, New York, New York 10027, 2 Skirball Institute,
New York University Medical Center, New York, New York 10016, and
3 Department of Biochemistry, Center for Molecular
Neuroscience, Vanderbilt University Medical School, Nashville,
Tennessee 37232
In addition to its role as a survival factor, nerve growth factor
(NGF) has been implicated in initiating apoptosis in restricted cell
types both during development and after terminal cell differentiation. NGF binds to the TrkA tyrosine kinase and the p75 neurotrophin receptor, a member of the tumor necrosis factor cytokine family. To
understand the mechanisms underlying survival versus death decisions,
the TrkA receptor was introduced into oligodendrocyte cell cultures
that undergo apoptosis in a p75-dependent manner. Here we report that
activation of the TrkA NGF receptor in oligodendrocytes negates cell
death by the p75 receptor. TrkA-mediated rescue from apoptosis
correlated with mitogen-activated protein kinase activation. Concurrently, activation of TrkA in oligodendrocytes resulted in
suppression of c-jun kinase activity initiated by p75, whereas induction of NF B activity by p75 was unaffected. These results indicate that TrkA-mediated rescue involves not only activation of
survival signals but also simultaneous suppression of a death signal by
p75. The selective interplay between tyrosine kinase and cytokine
receptors provides a novel mechanism that achieves alternative cellular
responses by merging signals from different ligand-receptor
systems.
Key words:
apoptosis; neurotrophins; receptor crosstalk; protein
kinase; oligodendrocyte; nerve growth factor
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893273-09$05.00/0
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M. Soilu-Hanninen, P. Ekert, T. Bucci, D. Syroid, P. F. Bartlett, and T. J. Kilpatrick
Nerve Growth Factor Signaling throu | |
