Multiple biological activities for two peptides derived from the nerve growth factor precursor.
ProNGF can be cleaved proteolytically at dibasic residues and liberates two other peptides beside NGF, LIP1 a 29 amino acid (aa) peptide and LIP2 a 38 aa peptide. These peptides were found present in the rat intestine and shown to induce rapid phosphorylation of the Trk receptor in cell lines. The present study describes several novel biological properties for these peptides. They exert an anti-proliferative effect on the mitogenic activity of estrogen and IGF in MCF-7 cells. They protect against in vivo induction of excitotoxic lesions by the glutamatergic analogue ibotenate injected into the developing mouse brain and against in vitro NMDA-induced cell death in primary neuronal cultures. They bind to murine microglial cells and induce phosphorylation of Akt. These results suggest a role for LIP1 and LIP2 in cell survival.
Dicou
Eleni
E
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, UMR 6097, Valbonne, France. dicou@ipmc.cnrs.fr
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002460:Cell Line; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology; D008938:Mitosis / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011498:Protein Precursors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D004967:Estrogens; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011498:Protein Precursors; D051057:Proto-Oncogene Proteins c-akt; D013002:Somatomedins; D000099183:Sortilin