Research article

Nucleolar localization of an isoform of the IGF-I precursor

Daniel SW Tan , Alexandra Cook and Shern L Chew

Department of Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London EC1A 7BE, United Kingdom

author email corresponding author email

BMC Cell Biology 2002, 3:17doi:10.1186/1471-2121-3-17

Published:	2 July 2002

Abstract

Background

Alternative exons encode different isoforms of the human insulin-like growth factor-I (IGF-I) precursor without altering mature IGF-I. We hypothesized that the various IGF-I precursors may traffic IGF-I differently. Chimeric IGF-I precursors were made with green fluorescent protein (GFP) cloned between the signal and mature IGF-I domains.

Results

Chimeras containing exons 1 or 2 were located in the cytoplasm, consistent with a secretory pathway, and suggesting that both exons encoded functional signal peptides. Exon 5-containing chimeras localized to the nucleus and strongly to the nucleolus, while chimeras containing exon 6 or the upstream portion of exon 5 did not. Nuclear and nucleolar localization also occurred when the mature IGF-I domain was deleted from the chimeras, or when signal peptides were deleted.

Conclusions

We have identified a nucleolar localization for an isoform of the human IGF-I precursor. The findings are consistent with the presence of a nuclear and nucleolar localization signal situated in the C-terminal part of the exon 5-encoded domain with similarities to signals in several other growth factors.