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Volume 17, Number 16,
Issue of August 15, 1997
pp. 6031-6037
Copyright ©1997 Society for Neuroscience
Optimal Nerve Growth Factor Trophic Signals Mediated by Synergy
of TrkA and p75 Receptor-Specific Ligands
Received Nov. 8, 1996; revised May 16, 1997; accepted May 28, 1997.
Sergei Maliartchouk1 and
H. Uri Saragovi1, 2
1 Department of Pharmacology and Therapeutics and
2 Cancer Centre, McGill University,
Montréal, Québec, Canada H3G 1Y6
Nerve growth factor (NGF) receptor-mediated signaling was studied
using specific monoclonal antibodies (mAbs) as ligands that discriminate between the receptors TrkA and p75. mAb-induced trophic signals were compared with the signals of the natural ligand NGF. In
cells expressing TrkA but no p75 receptors (TrkA+
p75 ), binding of TrkA with mAb 5C3 leads to
optimal signals. In cells expressing both TrkA and p75
(TrkA+ p75+), binding of TrkA
with mAb 5C3 leads to significant but suboptimal signals, and optimal
trophic signals are obtained by concomitant binding of TrkA and p75
with mAbs 5C3 and MC192. In TrkA+
p75+ cells, binding of anti-p75 mAb MC192 also
enhances the trophic effect of suboptimal concentrations of NGF. In
contrast, in cells expressing p75 receptors singly
(TrkA p75+), binding with mAb
MC192 or NGF causes very limited or no trophic effects. Thus, the data
support the hypothesis that unbound p75 may modulate TrkA trophic
signals. Importantly, the data also demonstrate for the first time that
in multireceptor systems appropriate combinations of anti-receptor mAbs
can fully mimic the signals of a polypeptide growth factor.
Key words:
NGF;
receptor;
TrkA;
p75;
trophic signals;
agonist;
ligand;
mAb
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