ArticleOpen biology2012
Evolution of signal multiplexing by 14-3-3-binding 2R-ohnologue protein families in the vertebrates.
Article in Open biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation.The EMBO journal · 2026Article
- TBC1D1 functions as a negative regulator of satellite cells for muscle regeneration.Nature communications · 2025Article
- Look for the Scaffold: Multifaceted Regulation of Enzyme Activity by 14-3-3 Proteins.Physiological research · 2024Review
- Evolution of the Spider Homeobox Gene Repertoire by Tandem and Whole Genome Duplication.Molecular biology and evolution · 2023Article
- Article
- 14-3-3 Proteins are Potential Regulators of Liquid-Liquid Phase Separation.Cell biochemistry and biophysics · 2022Review
- Shotgun and TMT-Labeled Proteomic Analysis of the Ovarian Proteins of an Insect Vector, Aedes aegypti (Diptera: Culicidae).Journal of insect science (Online) · 2022Article
- Reticulon-like REEP4 at the inner nuclear membrane promotes nuclear pore complex formation.The Journal of cell biology · 2022Article
- Amphioxus muscle transcriptomes reveal vertebrate-like myoblast fusion genes and a highly conserved role of insulin signalling in the metabolism of muscle.BMC genomics · 2022Article
- Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?Frontiers in molecular biosciences · 2022Review
- Identification of HCN1 as a 14-3-3 client.PloS one · 2022Article
- Region-specific expression of young small-scale duplications in the human central nervous system.BMC ecology and evolution · 2021Article
- Importance of lipids for upper motor neuron health and disease.Seminars in cell & developmental biology · 2021Review
- Using phosphoproteomics data to understand cellular signaling: a comprehensive guide to bioinformatics resources.Clinical proteomics · 2020Review
- Analysis of 14-3-3 isoforms expressed in photoreceptors.Experimental eye research · 2018Article
- Keeping the home fires burning: AMP-activated protein kinase.Journal of the Royal Society, Interface · 2018Review
- GFAP expression in injured astrocytes in rats.Experimental and therapeutic medicine · 2017Article
- Recent advances in understanding the roles of whole genome duplications in evolution.F1000Research · 2017Review
- Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa.American journal of human genetics · 2016Article
- AMP-activated protein kinase: a cellular energy sensor that comes in 12 flavours.The FEBS journal · 2016Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
14-3-3 proteins regulate cellular responses to stimuli by docking onto pairs of phosphorylated residues on target proteins. The present study shows that the human 14-3-3-binding phosphoproteome is highly enriched in 2R-ohnologues, which are proteins in families of two to four members that were generated by two rounds of whole genome duplication at the origin of the vertebrates. We identify 2R-ohnologue families whose members share a 'lynchpin', defined as a 14-3-3-binding phosphosite that is conserved across members of a given family, and aligns with a Ser/Thr residue in pro-orthologues from the invertebrate chordates. For example, the human receptor expression enhancing protein (REEP) 1-4 family has the commonest type of lynchpin motif in current datasets, with a phosphorylatable serine in the -2 position relative to the 14-3-3-binding phosphosite. In contrast, the second 14-3-3-binding sites of REEPs 1-4 differ and are phosphorylated by different kinases, and hence the REEPs display different affinities for 14-3-3 dimers. We suggest a conceptual model for intracellular regulation involving protein families whose evolution into signal multiplexing systems was facilitated by 14-3-3 dimer binding to lynchpins, which gave freedom for other regulatory sites to evolve. While increased signalling complexity was needed for vertebrate life, these systems also generate vulnerability to genetic disorders.
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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.