Two peptides derived from the nerve growth factor precursor are biologically active

Eleni Dicou, Beth Pflug, Marilyn Magazin, Thérèse Lehy, Daniel Djakiew, Pascual Ferrara, Véronique Nerrière, Douglas Harvie

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This report provides evidence that the proregion of the NGF precursor protein contains two novel peptides. The presence of pairs of basic amino acid (aa) residues in the NGF proregion suggests that two or three peptides other than NGF may be generated by proteolytic cleavage. Synthetic peptides of 29 aa (LIP1) and 38aa (LIP2) corresponding to the sequences -71 to -43 and -40 to -3 of the proNGF, respectively, were used in this study. ELISA specific for these two peptides revealed their presence in the rat intestine. LIP1 was localized by immunohistochemistry in endocrine cells of the intestinal epithelium, and LIP2 was immunoprecipitated from an intestinal extract. We also provide evidence for the presence of specific receptors for LIP2 in several cell lines. Scatchard analysis indicated the presence of a low affinity binding site with a K(d) of ~10-7 M and a high affinity binding site of 10-9 M. Cross-linking studies revealed receptors forms of about 140 kd and 93 kD in a prostatic adenocarcinoma cell line. LIP1 nd LIP2 induced rapid F-actin redistribution in PC12 cells within 2 min of incubation, which suggests a role of LIP1 and LIP2 in the process of neurite outgrowth. Furthermore, both propeptides induced rapid tyrosine phosphorylation of the Trk protein in both prostatic adenocarcinoma cells and PC12 cells, thus implicating trk in their mechanism of action. These results support our hypothesis that two peptides within the NGF precursor protein are biologically active.

Original languageEnglish (US)
Pages (from-to)389-398
Number of pages10
JournalJournal of Cell Biology
Issue number2
StatePublished - Feb 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    Dicou, E., Pflug, B., Magazin, M., Lehy, T., Djakiew, D., Ferrara, P., Nerrière, V., & Harvie, D. (1997). Two peptides derived from the nerve growth factor precursor are biologically active. Journal of Cell Biology, 136(2), 389-398.