Nucleolar localization of an isoform of the IGF-I precursor.
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.
Tan
Daniel S-W
DS
Department of Endocrinology, St Bartholomew's Hospital, Queen Mary, Universityof London, United Kingdom. dswtan@hotmail.com
Cook
Alexandra
A
Chew
Shern L
SL
D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D049452:Green Fluorescent Proteins; D006367:HeLa Cells / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007438:Introns / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008164:Luminescent Proteins; D020033:Protein Isoforms; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I