Effects of a Peptide Analogue of the Amphiphilic Domain of the Common Neurotrophin Receptor on Nerve Growth Factor‐Mediated Motility of Human Neuroblastoma Cells

• Published in: Journal of neurochemistry 1998-06, Vol.70 (6), p.2327-2335
• Main Authors: Wang, Wei, Dostaler, Suzanne M., Lawrance, Gail, Ross, Gregory M., Riopelle, Richard J., Dow, Kimberly E.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Movement - drug effects; Cell Movement - physiology; Cell receptors; Cell structures and functions; Cell Survival - drug effects; Cross-Linking Reagents - chemistry; Culture Media, Serum-Free; Fundamental and applied biological sciences. Psychology; GAP-43 Protein - biosynthesis; Humans; Invasion; Miscellaneous; Molecular and cellular biology; Nerve growth factor; Nerve Growth Factors - metabolism; Nerve Growth Factors - physiology; Neurite growth; Neurites - drug effects; Neurites - physiology; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neuroblastoma - ultrastructure; p75NTR; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Phosphorylation; Polymerase Chain Reaction; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Receptor Protein-Tyrosine Kinases - biosynthesis; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases - physiology; Receptor, Nerve Growth Factor; Receptor, trkA; Receptors, Nerve Growth Factor - biosynthesis; Receptors, Nerve Growth Factor - chemistry; Receptors, Nerve Growth Factor - metabolism; Receptors, Nerve Growth Factor - physiology; RNA, Messenger - biosynthesis; trkA; Tumor Cells, Cultured
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.70062327.x

: Exposure of human neuroblastoma cells (IMR‐32) to a peptide mimic of the cytoplasmic amphiphilic domain of the common neurotrophin receptor (p75NTR 367–379) resulted in enhanced nerve growth factor (NGF)‐mediated inhibition of cell invasion in vitro. The peptide also enhanced NGF‐mediated neurite extension and GAP‐43 gene expression but had no effect on NGF‐mediated cell survival. These latter functional effects mimicked influences on NGF‐mediated neurite growth in other trkA‐positive cells as reported previously. NGF‐dependent trkA phosphorylation was significantly enhanced by the presence of the peptide, whereas high‐affinity binding of 125I‐NGF, both NGF receptors mRNA and protein expression, and trkA dimer/monomer ratios were not influenced. The studies suggest that ligand‐mediated trkA activation has differential effects on cell motility phenomena and that the amphiphilic domain of p75NTR has a role in this differential signaling.