Gregoire F M, Chomiki N, Kachinskas D, Warden C H
Rowe Genetics Program, University of California at Davis, Davis, California, 95616, USA.
Biochem Biophys Res Commun. 1998 Aug 19;249(2):385-90. doi: 10.1006/bbrc.1998.9164.
Aging, metabolism and fat accumulation in Caenorhabditis elegans (C. elegans) are influenced by mutations in DAF-2, a putative insulin-like receptor. Ten putative insulin-like genes have been recently identified from the C. elegans genome database. However, it is unclear if these genes are orthologues of human insulin since they lack the C-peptide dibasic amino acid proteolysis sites. We have identified and measured mRNA expression during development of two novel members of the C. elegans insulin-like gene family. We also report the sequence characterization and gene structure for one of these, the insulin-like protein-1 (ILP1). We focused on ILP1 characterization because it has structural features consistent with its being a candidate insulin ligand for the DAF-2 insulin-like receptor. For example, ILP1 has a putative C-peptide flanked by dibasic amino acids, exhibits conserved cysteine residues that could provide disulfide bonds between the A and B chains, and has two introns. Northern blot analysis revealed that ILP1 mRNA is expressed at very high levels in embryos and is downregulated very early during postnatal development, suggesting that it may influence embryonic development, but not Dauer formation. We also identified a novel insulin-like growth factor-1-like protein (T28B8/IGF-I) that exhibits a very different developmental expression profile than ILP1. Our results are consistent with the hypothesis that members of the unusually large and complex C. elegans insulin-like protein family exhibit complex and perhaps redundant roles.
秀丽隐杆线虫（C. elegans）的衰老、新陈代谢和脂肪积累受DAF-2（一种假定的胰岛素样受体）突变的影响。最近从秀丽隐杆线虫基因组数据库中鉴定出了10个假定的胰岛素样基因。然而，由于这些基因缺乏C肽双碱性氨基酸蛋白水解位点，它们是否为人胰岛素的直系同源基因尚不清楚。我们鉴定并测量了秀丽隐杆线虫胰岛素样基因家族两个新成员在发育过程中的mRNA表达。我们还报告了其中一个基因——胰岛素样蛋白-1（ILP1）的序列特征和基因结构。我们专注于ILP1的特征分析，因为它具有的结构特征表明其可能是DAF-2胰岛素样受体的胰岛素配体候选物。例如，ILP1有一个两侧为双碱性氨基酸的假定C肽，具有保守的半胱氨酸残基，可在A链和B链之间提供二硫键，并且有两个内含子。Northern印迹分析显示，ILP1 mRNA在胚胎中高水平表达，并在出生后发育早期被下调，这表明它可能影响胚胎发育，但不影响 dauer 形成。我们还鉴定出一种新型胰岛素样生长因子-1样蛋白（T28B8/IGF-I），其发育表达谱与ILP1非常不同。我们的结果与以下假设一致：异常庞大且复杂的秀丽隐杆线虫胰岛素样蛋白家族成员发挥着复杂且可能冗余的作用。
