ArticleNature chemical biology2019
Extracellular phosphorylation drives the formation of neuronal circuitry.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
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- An Introduction to Analytical Challenges, Approaches, and Applications in Mass Spectrometry-Based Secretomics.Molecular & cellular proteomics : MCP · 2023Review
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- Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome.Cellular and molecular life sciences : CMLS · 2023Article
- Regulation of secretory pathway kinase or kinase-like proteins in human cancers.Frontiers in immunology · 2023Review
- Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A natural carotenoid crocin exerts antidepressant action by promoting adult hippocampal neurogenesis through Wnt/β-catenin signaling.Journal of advanced research · 2023Article
- Cbln1 regulates axon growth and guidance in multiple neural regions.PLoS biology · 2022Article
- Vertebrate lonesome kinase modulates the hepatocyte secretome to prevent perivascular liver fibrosis and inflammation.Journal of cell science · 2022Article
- The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation.Blood · 2022Article
- Dysfunction of the Hippocampal-Lateral Septal Circuit Impairs Risk Assessment in Epileptic Mice.Frontiers in molecular neuroscience · 2022Article
- Proteolytic processing of secretory pathway kinase Fam20C by site-1 protease promotes biomineralization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Until recently, the existence of extracellular kinase activity was questioned. Many proteins of the central nervous system are targeted, but it remains unknown whether, or how, extracellular phosphorylation influences brain development. Here we show that the tyrosine kinase vertebrate lonesome kinase (VLK), which is secreted by projecting retinal ganglion cells, phosphorylates the extracellular protein repulsive guidance molecule b (RGMb) in a dorsal-ventral descending gradient. Silencing of VLK or RGMb causes aberrant axonal branching and severe axon misguidance in the chick optic tectum. Mice harboring RGMb with a point mutation in the phosphorylation site also display aberrant axonal pathfinding. Mechanistic analyses show that VLK-mediated RGMb phosphorylation modulates Wnt3a activity by regulating LRP5 protein gradients. Thus, the secretion of VLK by projecting neurons provides crucial signals for the accurate formation of nervous system circuitry. The dramatic effect of VLK on RGMb and Wnt3a signaling implies that extracellular phosphorylation likely has broad and profound effects on brain development, function and disease.
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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.