EFFECTS OF A PEPTIDE ANALOG OF THE AMPHIPHILIC DOMAIN OF THE COMMON NEUROTROPHIN RECEPTOR ON NERVE GROWTH FACTOR-MEDIATED MOTILITY OF HUMANNEUROBLASTOMA-CELLS

Exposure of human neuroblastoma cells (IMR-32) to a peptide mimic of t he cytoplasmic amphiphilic domain of the common neurotrophin receptor (p75(NTR) 367-379) resulted in enhanced nerve growth factor (NGF)-medi ated inhibition of cell invasion in vitro. The peptide also enhanced N GF-mediated neurite extension and GAP-43 gene expression but had no ef fect on NGF-mediated cell survival. These latter functional effects mi micked influences on NGF-mediated neurite growth in other trkA-positiv e cells as reported previously. NGF-dependent trkA phosphorylation was significantly enhanced by the presence of the peptide, whereas high-a ffinity binding of I-125-NGF, both NGF receptors mRNA and protein expr ession, 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 p75(NTR ) has a role in this differential signaling.