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J Biol Chem, Vol. 273, Issue 52, 34933-34940, December 25, 1998
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From the Nerve growth factor (NGF) is a neurotrophin that
induces neuritogenic and trophic signals by binding to TrkA and/or p75
receptors. We report a comparative study of the binding,
internalization, and biological activity of NGF versus that
of NGF in association with an anti-NGF monoclonal antibody (mAb NGF30),
directed against the C termini of NGF. NGF·mAb complexes do not bind
p75 effectively but bind TrkA with high affinity. After binding,
NGF·mAb complexes stimulate internalization faster and to a larger
degree than NGF. NGF·mAb-induced activation of TrkA, Shc, and MAPK is
transient compared with NGF-induced activation; yet NGF and NGF·mAb
afford identical trophic responses. In contrast, NGF induces
Suc-1-associated neurotrophic activating protein phosphorylation and
neuritogenic differentiation, but NGF·mAb does not. Thus, an absolute
separation of trophic and neuritogenic function is seen for NGF·mAb,
suggesting that biological response modifiers of neurotrophins can
afford ligands with selected activities.
Department of Pharmacology and Therapeutics,
§ Oncology/Cancer Center, and
Department of Cell
Biology,
Department of Biological Chemistry,
Finch University of Health Sciences/The Chicago Medical School,
North Chicago, Illinois 60064
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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