ArticlePloS one2016
Mechanism of Action of Secreted Newt Anterior Gradient Protein.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 28 citations in OpenAlex.
- Neuronal activation in the axolotl brain promotes tail regeneration.NPJ Regenerative medicine · 2025Article
- The salamander blastema within the broader context of metazoan regeneration.Frontiers in cell and developmental biology · 2023Review
- Positional Memory in Vertebrate Regeneration: A Century's Insights from the Salamander Limb.Cold Spring Harbor perspectives in biology · 2022Review
- MAPK/ERK Pathway as a Central Regulator in Vertebrate Organ Regeneration.International journal of molecular sciences · 2022Review
- Post-amputation reactive oxygen species production is necessary for axolotls limb regeneration.Frontiers in cell and developmental biology · 2022Article
- The nervous system: Orchestra conductor in cancer, regeneration, inflammation and immunity.FASEB bioAdvances · 2021Review
- Salamanders: The molecular basis of tissue regeneration and its relevance to human disease.Current topics in developmental biology · 2021Review
- The Secreted Protein Disulfide Isomerase Ag1 Lost by Ancestors of Poorly Regenerating Vertebrates Is Required forFrontiers in cell and developmental biology · 2021Article
- Secretion of pro-oncogenic AGR2 protein in cancer.Heliyon · 2020Review
- Nerves in cancer.Nature reviews. Cancer · 2020Review
- Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes.Journal of extracellular vesicles · 2018Article
- Generic wound signals initiate regeneration in missing-tissue contexts.Nature communications · 2017Article
- ITRAQ-based quantitative proteomic analysis of Cynops orientalis limb regeneration.BMC genomics · 2017Article
- Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Role of the Prod1 Membrane Anchor in Newt Limb Regeneration.Angewandte Chemie (International ed. in English) · 2017Article
- A brief history of the study of nerve dependent regeneration.Neurogenesis (Austin, Tex.) · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Anterior gradient (AG) proteins have a thioredoxin fold and are targeted to the secretory pathway where they may act in the ER, as well as after secretion into the extracellular space. A newt member of the family (nAG) was previously identified as interacting with the GPI-anchored salamander-specific three-finger protein called Prod1. Expression of nAG has been implicated in the nerve dependence of limb regeneration in salamanders, and nAG acted as a growth factor for cultured newt limb blastemal (progenitor) cells, but the mechanism of action was not understood. Here we show that addition of a peptide antibody to Prod1 specifically inhibit the proliferation of blastema cells, suggesting that Prod1 acts as a cell surface receptor for secreted nAG, leading to S phase entry. Mutation of the single cysteine residue in the canonical active site of nAG to alanine or serine leads to protein degradation, but addition of residues at the C terminus stabilises the secreted protein. The mutation of the cysteine residue led to no detectable activity on S phase entry in cultured newt limb blastemal cells. In addition, our phylogenetic analyses have identified a new Caudata AG protein called AG4. A comparison of the AG proteins in a cell culture assay indicates that nAG secretion is significantly higher than AGR2 or AG4, suggesting that this property may vary in different members of the family.
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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.