ArticleThe Journal of biological chemistry2010
HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 48 citations in OpenAlex.
- The role of the RS1-NEDD4-YAP1 axis orchestrates epithelial-macrophage interplay in COPD.Respiratory research · 2026Article
- Sprouty in Tumors of the Nervous System.International journal of molecular sciences · 2025Review
- Article
- PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.Oncogenesis · 2023Article
- MNK Proteins as Therapeutic Targets in Leukemia.OncoTargets and therapy · 2023Review
- Hsa-miR-22-3p inhibits liver cancer cell EMT and cell migration/ invasion by indirectly regulating SPRY2.PloS one · 2023Article
- Lycorine suppresses cell growth and invasion via down-regulation of NEDD4 ligase in bladder cancer.American journal of cancer research · 2022Article
- A Sprouty4 Mutation Identified in Kallmann Syndrome Increases the Inhibitory Potency of the Protein towards FGF and Connected Processes.International journal of molecular sciences · 2021Article
- Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.PloS one · 2021Article
- Identification of key features required for efficient S-acylation and plasma membrane targeting of sprouty-2.Journal of cell science · 2020Article
- The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma.International journal of molecular sciences · 2020Review
- Tracing Potential Covalent Inhibitors of an E3 Ubiquitin Ligase through Target-Focused Modelling.Molecules (Basel, Switzerland) · 2019Article
- Simultaneous Knockdown of Sprouty2 and PTEN Promotes Axon Elongation of Adult Sensory Neurons.Frontiers in cellular neuroscience · 2019Article
- Exploring the Structural Mechanism of Covalently Bound E3 Ubiquitin Ligase: Catalytic or Allosteric Inhibition?The protein journal · 2018Article
- Whole exome sequencing in adult-onset hearing loss reveals a high load of predicted pathogenic variants in known deafness-associated genes and identifies new candidate genes.BMC medical genomics · 2018Article
- Genome-Wide Association Study Links Receptor Tyrosine Kinase Inhibitor Sprouty 2 to Thrombocytopenia after Coronary Artery Bypass Surgery.Thrombosis and haemostasis · 2018Article
- Encoding human serine phosphopeptides in bacteria for proteome-wide identification of phosphorylation-dependent interactions.Nature biotechnology · 2018Article
- Hypoxia inducible factors regulate the transcription of the sprouty2 gene and expression of the sprouty2 protein.PloS one · 2017Article
- Sprouty2 Protein Regulates Hypoxia-inducible Factor-α (HIFα) Protein Levels and Transcription of HIFα-responsive Genes.The Journal of biological chemistry · 2016Article
- SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150.Oncogene · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Sprouty (Spry) proteins are important regulators of receptor tyrosine kinase signaling in development and disease. Alterations in cellular Spry content have been associated with certain forms of cancers and also in cardiovascular diseases. Thus, understanding the mechanisms that regulate cellular Spry levels are important. Herein, we demonstrate that Spry1 and Spry2, but not Spry3 or Spry4, associate with the HECT domain family E3 ubiquitin ligase, Nedd4. The Spry2/Nedd4 association involves the WW domains of Nedd4 and requires phosphorylation of the Mnk2 kinase sites, Ser(112) and Ser(121), on Spry2. The phospho-Ser(112/121) region on Spry2 that binds WW domains of Nedd4 is a novel non-canonical WW domain binding region that does not contain Pro residues after phospho-Ser. Endogenous and overexpressed Nedd4 polyubiquitinate Spry2 via Lys(48) on ubiquitin and decrease its stability. Silencing of endogenous Nedd4 increased the cellular Spry2 content and attenuated fibroblast growth factor-elicited ERK1/2 activation that was reversed when elevations in Spry2 levels were prevented by Spry2-specific small interfering RNA. Mnk2 silencing decreased Spry2-Nedd4 interactions and also augmented the ability of Spry2 to inhibit fibroblast growth factor signaling. This is the first report demonstrating the regulation of cellular Spry content and its ability to modulate receptor tyrosine kinase signaling by a HECT domain-containing E3 ubiquitin ligase.
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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.