Effects of a peptide analogue of the amphiphilic domain of the common neurotrophin receptor on nerve growth factor-mediated motility of human neuroblastoma cells.
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.
Wang
W
W
Department of Pediatrics, Queen's University, Kingston, Ontario, Canada.
Dostaler
S M
SM
Lawrence
G
G
Ross
G M
GM
Riopelle
R J
RJ
Dow
K E
KE
D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D016895:Culture Media, Serum-Free; D019922:GAP-43 Protein / Q000096:biosynthesis; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D016895:Culture Media, Serum-Free; D019922:GAP-43 Protein; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA