This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lebacq-Verheyden, A M Articles by Battey, J F Search for Related Content PubMed PubMed Citation Articles by Lebacq-Verheyden, A M Articles by Battey, J F

Posttranslational processing of endogenous and of baculovirus-expressed human gastrin-releasing peptide precursor.

Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20814.

ABSTRACT

The 27-amino-acid gastrin-releasing peptide (GRP1-27) is a neuropeptide and growth factor that is synthesized by various neural and neuroendocrine cells. The major pro-GRP hormone (isoform I) contains both GRP1-27 and a novel C-terminal extension peptide termed pro-GRP31-125. In order to define potentially active neuropeptides that could be generated from this novel protein domain, we analyzed the posttranslational processing of endogenous human pro-GRP1-125 in a small-cell lung cancer cell line. Because such studies are much easier in an overexpression system, we investigated at the same time the posttranslational processing of baculovirus-expressed human pro-GRP1-125 in an insect ovary cell line. In the small-cell lung cancer cell line, GRP1-27 was cleaved as expected from the endogenous prohormone at a pair of basic amino acids (29 and 30) and alpha-amidated at its C-terminal methionine; however, a number of novel peptides were generated by additional cleavages in the pro-GRP31-125 domain. In the insect ovary cell line, GRP1-27 was cleaved from the expressed prohormone by a different mechanism, as were a number of other peptides that appeared to be similar in size to those produced by the human neuroendocrine tumor cell line. These data show for the first time that an insect ovary cell line that is widely used to overexpress proteins can process a human neuropeptide precursor. They also reveal the existence of novel pro-GRP-derived peptides that are candidates for biologically active ligands.

This article has been cited by other articles:

• Patel, O., Dumesny, C., Shulkes, A., Baldwin, G. S. (2007). C-Terminal Fragments of the Gastrin-Releasing Peptide Precursor Stimulate Cell Proliferation via a Novel Receptor. Endocrinology 148: 1330-1339 [Abstract] [Full Text]  
• Zschenker, O., Oezden, D., Ameis, D. (2004). Lysosomal Acid Lipase as a Preproprotein. J Biochem 136: 65-72 [Abstract] [Full Text]  
• Li, C.-M., Adler, K. B., Cheng, P.-W. (1998). Mucin Biosynthesis: Molecular Cloning and Expression of Bovine Lung Mucin Core 2 N-Acetylglucosaminyltransferase cDNA. Am. J. Respir. Cell Mol. Bio. 18: 343-352 [Abstract] [Full Text]  
• You, L., Jakowlew, S. B. (1997). Identification of Early Growth Response Gene-1 (Egr-1) as a Phorbol Myristate Acetate-induced Gene in Lung Cancer Cells by Differential mRNA Display. Am. J. Respir. Cell Mol. Bio. 17: 617-624 [Abstract] [Full Text]