ArticleEndocrinology2013
Structural and functional analysis of the amphioxus IGFBP gene uncovers ancient origin of IGF-independent functions.
Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- What comparative endocrinology tells us about the original function of the insulin superfamily.Endocrine journal · 2025Review
- The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System.Genome biology and evolution · 2025Article
- Redefining the Tea Green Leafhopper:Life (Basel, Switzerland) · 2025Review
- Low-affinity insulin-like growth factor binding protein 7 and its association with pulmonary arterial hypertension severity and survival.Pulmonary circulation · 2023Article
- Proteomics discovery of pulmonary hypertension biomarkers: Insulin-like growth factor binding proteins are associated with disease severity.Pulmonary circulation · 2022Article
- The Origination of Growth Hormone/Insulin-Like Growth Factor System: A Story From Ancient Basal Chordate Amphioxus.Frontiers in endocrinology · 2022Review
- Insulin-like growth factors: Ligands, binding proteins, and receptors.Molecular metabolism · 2021Review
- Structural Lessons From the Mutant Proinsulin Syndrome.Frontiers in endocrinology · 2021Review
- Insulin-Like Growth Factor Binding Protein-5 in Physiology and Disease.Frontiers in endocrinology · 2020Review
- IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?Frontiers in endocrinology · 2018Review
- Insulin-Like Growth Factor-Binding Proteins of Teleost Fishes.Frontiers in endocrinology · 2018Review
- Lamprey IGF-Binding Protein-3 Has IGF-Dependent and -Independent Actions.Frontiers in endocrinology · 2016Article
- Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides.Cellular and molecular life sciences : CMLS · 2016Review
- Identification, evolution and expression of an insulin-like peptide in the cephalochordate Branchiostoma lanceolatum.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
IGFs play key roles in regulating vertebrate development, growth, reproduction, and aging. In extracellular fluids, IGFs are bound and regulated by a family of IGF-binding proteins (IGFBPs). Although all known IGFBPs are secreted proteins, some are also found in the nucleus and possess IGF-independent activities. When and how these distinct modes of biological actions have evolved is unknown. In this study, we identified and analyzed an IGFBP gene from amphioxus. Amphioxus shares a common ancestor with the modern vertebrate lineage that dates back to more than 520 million years ago. The amphioxus IGFBP shares all major structural characteristics of vertebrate IGFBPs. Phylogenetic analyses place it in a basal position in the IGFBP lineage. Ligand blot analysis reveals that amphioxus IGFBP does not bind to IGF-I or -II. Changing its Phe70 into Leu, however, is sufficient to convert it into a functional IGF binder. When tested in cultured cells, amphioxus IGFBP is localized in the nucleus, and this is attributed to 2 redundant nuclear localization sequences in its L domain. Furthermore, the amphioxus IGFBP N-terminal domain has strong transcriptional activation activity. Forced expression of amphioxus IGFBP in zebrafish embryos results in dorsalized phenotypes. This action requires nuclear localization. These results suggest that the nuclear localization and transcription activation activity of IGFBPs are ancient functions and the IGF-binding function may have been acquired by opportunistic gain-of-functional mutations later in evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.