 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 13, 2919-2929, Copyright © 1993 by Society for Neuroscience
Transfection with trk restores "slow" NGF binding, efficient NGF uptake, and multiple NGF responses to NGF-nonresponsive PC12 cell mutants
DM Loeb and LA Greene
Department of Pathology, Columbia University, New York, New York 10032.
NGF binds to and activates the protein tyrosine kinase gp 140prototrk.
Expression of this receptor is required for at least some responses to NGF.
Three outstanding issues are addressed in the present work. First, we
determined whether expression of gp 140prototrk is required for all
neuronal NGF responses. Second, we examined the role of gp 140prototrk in
NGF binding and internalization. Third, we addressed the utility of
NGF-nonresponsive PC12nnr5 cells for study of the NGF mechanism. In
contrast to wild-type PC12 cells, PC12nnr5 cells do not express endogenous
gp 140prototrk. We therefore asked whether they possess other defects that
compromise NGF signaling pathways. To answer these questions, we
transfected PC12nnr5 cells with a cDNA encoding full- length human gp
140prototrk and isolated cell lines permanently expressing the receptor.
Introduction of trk rescued all of the many and varied NGF responses
assessed, including enhanced protein tyrosine phosphorylation, induction of
immediate-early and neural-specific genes, neurite outgrowth and
regeneration, maintenance of survival in serum-free medium, and stimulation
of AChE activity. In contrast to PC12nnr5 cells, the trk-transfected lines
also bind and internalize NGF with wild-type PC12 cell characteristics.
These findings indicate that gp 140prototrk is required for many, if not
all, responses of neuronal cells to NGF and is necessary for proper NGF
binding and internalization. Additionally, as no signaling defect other
than the absence of trk expression was revealed in PC12nnr5 cells, this
work supports the utility of this line for genetic dissection of the NGF
mechanism of action.
This article has been cited by other articles:
|
|
|
|
 
D. K. Parran, A. Barker, and M. Ehrich
Effects of Thimerosal on NGF Signal Transduction and Cell Death in Neuroblastoma Cells
Toxicol. Sci.,
July 1, 2005;
86(1):
132 - 140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-w. K. Wu and H. H. Yeh
Nerve Growth Factor Rapidly Increases Muscarinic Tone in Mouse Medial Septum/Diagonal Band of Broca
J. Neurosci.,
April 27, 2005;
25(17):
4232 - 4242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Ryu, H. P. Harding, J. M. Angelastro, O. V. Vitolo, D. Ron, and L. A. Greene
Endoplasmic Reticulum Stress and the Unfolded Protein Response in Cellular Models of Parkinson's Disease
J. Neurosci.,
December 15, 2002;
22(24):
10690 - 10698.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Miranda, M. Di Virgilio, S. Selleri, G. Zanotti, S. Pagliardini, M. A. Pierotti, and A. Greco
Novel Pathogenic Mechanisms of Congenital Insensitivity to Pain with Anhidrosis Genetic Disorder Unveiled by Functional Analysis of Neurotrophic Tyrosine Receptor Kinase Type 1/Nerve Growth Factor Receptor Mutations
J. Biol. Chem.,
February 15, 2002;
277(8):
6455 - 6462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Beattie, C. L. Howe, A. Wilde, F. M. Brodsky, and W. C. Mobley
NGF Signals through TrkA to Increase Clathrin at the Plasma Membrane and Enhance Clathrin-Mediated Membrane Trafficking
J. Neurosci.,
October 1, 2000;
20(19):
7325 - 7333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Angelastro, L. Klimaschewski, S. Tang, O. V. Vitolo, T. A. Weissman, L. T. Donlin, M. L. Shelanski, and L. A. Greene
Identification of diverse nerve growth factor-regulated genes by serial analysis of gene expression (SAGE) profiling
PNAS,
September 12, 2000;
97(19):
10424 - 10429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. Romero, N. Rangappa, L. Li, E. Lightfoot, M. G. Garry, and G. M. Smith
Extensive Sprouting of Sensory Afferents and Hyperalgesia Induced by Conditional Expression of Nerve Growth Factor in the Adult Spinal Cord
J. Neurosci.,
June 15, 2000;
20(12):
4435 - 4445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Walsh, K. M. Krol, K. A. Crutcher, and M. D. Kawaja
Enhanced Neurotrophin-Induced Axon Growth in Myelinated Portions of the CNS in Mice Lacking the p75 Neurotrophin Receptor
J. Neurosci.,
May 15, 1999;
19(10):
4155 - 4168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Walsh, K. M. Krol, and M. D. Kawaja
Absence of the p75 Neurotrophin Receptor Alters the Pattern of Sympathosensory Sprouting in the Trigeminal Ganglia of Mice Overexpressing Nerve Growth Factor
J. Neurosci.,
January 1, 1999;
19(1):
258 - 273.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Mutoh, A. Tokuda, J.-i. Inokuchi, and M. Kuriyama
Glucosylceramide Synthase Inhibitor Inhibits the Action of Nerve Growth Factor in PC12 Cells
J. Biol. Chem.,
October 2, 1998;
273(40):
26001 - 26007.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Urdiales, E. Becker, M. Andrieu, A. Thomas, J. Jullien, L. A. van Grunsven, S. Menut, G. I. Evan, D. Martin-Zanca, and B. B. Rudkin
Cell Cycle Phase-Specific Surface Expression of Nerve Growth Factor Receptors TrkA and p75NTR
J. Neurosci.,
September 1, 1998;
18(17):
6767 - 6775.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Zapf-Colby and J. M. Olefsky
Nerve Growth Factor Processing and Trafficking Events Following TrkA-Mediated Endocytosis
Endocrinology,
July 1, 1998;
139(7):
3232 - 3240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Senger and R. B. Campenot
Rapid Retrograde Tyrosine Phosphorylation of trkA and Other Proteins in Rat Sympathetic Neurons in Compartmented Cultures
J. Cell Biol.,
July 28, 1997;
138(2):
411 - 421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. T. Sherwood, S. S. Lesser, and D. C. Lo
Neurotrophin regulation of ionic currents and cell size depends on cell context
PNAS,
May 27, 1997;
94(11):
5917 - 5922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lazarovici, M. Oshima, D. Shavit, M. Shibutani, H. Jiang, M. Monshipouri, D. Fink, V. Movsesyan, and G. Guroff
Down-regulation of Epidermal Growth Factor Receptors by Nerve Growth Factor in PC12 Cells Is p140trk-, Ras-, and Src-dependent
J. Biol. Chem.,
April 25, 1997;
272(17):
11026 - 11034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Grimes, J. Zhou, E. C. Beattie, E. C. Yuen, D. E. Hall, J. S. Valletta, K. S. Topp, J. H. LaVail, N. W. Bunnett, and W. C. Mobley
Endocytosis of Activated TrkA: Evidence that Nerve Growth Factor Induces Formation of Signaling Endosomes
J. Neurosci.,
December 15, 1996;
16(24):
7950 - 7964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. De Bernardi, S. J. Rabin, A. M. Colangelo, G. Brooker, and I. Mocchetti
trkA Mediates the Nerve Growth Factor-induced Intracellular Calcium Accumulation
J. Biol. Chem.,
March 15, 1996;
271(11):
6092 - 6098.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Jör. M. Windisch, R. Marksteiner, and R. Schneider
Nerve Growth Factor Binding Site on TrkA Mapped to a Single 24-Amino Acid Leucine-rich Motif
J. Biol. Chem.,
November 24, 1995;
270(47):
28133 - 28138.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. LeSauteur, L. Wei, B. F. Gibbs, and H. U. Saragovi
Small Peptide Mimics of Nerve Growth Factor Bind TrkA Receptors and Affect Biological Responses
J. Biol. Chem.,
March 24, 1995;
270(12):
6564 - 6569.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Ferrari, B. L. Anderson, R. M. Stephens, D. R. Kaplan, and L. A. Greene
Prevention of Apoptotic Neuronal Death by G[IMAGE] Ganglioside
J. Biol. Chem.,
February 17, 1995;
270(7):
3074 - 3080.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
