ArticleThe Journal of biological chemistry2011
Regulation of cellular levels of Sprouty2 protein by prolyl hydroxylase domain and von Hippel-Lindau proteins.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- Loss of VHL-mediated pRb regulation promotes clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.Scientific reports · 2024Article
- SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.bioRxiv : the preprint server for biology · 2024Article
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.Oncogenesis · 2023Article
- PHD3 inhibits cell proliferation through hydroxylation of PAX2 at proline 9.Acta biochimica et biophysica Sinica · 2022Article
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation.Molecules (Basel, Switzerland) · 2021Review
- The pVHL neglected functions, a tale of hypoxia-dependent and -independent regulations in cancer.Open biology · 2020Review
- Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates.eLife · 2019Article
- Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors.PLoS computational biology · 2019Article
- Inhibition of cardiomyocyte Sprouty1 protects from cardiac ischemia-reperfusion injury.Basic research in cardiology · 2019Article
- Bexarotene - a novel modulator of AURKA and the primary cilium inJournal of cell science · 2018Article
- Regulation of vascular signalling by nuclear Sprouty2 in fetal lung epithelial cells: Implications for co-ordinated airway and vascular branching in lung development.Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology · 2018Article
- VHL and Hypoxia Signaling: Beyond HIF in Cancer.Biomedicines · 2018Review
- Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animalHypoxia (Auckland, N.Z.) · 2018Article
- Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and Potential Targeting for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Sprouty (Spry) proteins modulate the actions of receptor tyrosine kinases during development and tumorigenesis. Decreases in cellular levels of Spry, especially Sprouty2 (Spry2), have been implicated in the growth and progression of tumors of the breast, prostate, lung, and liver. During development and tumor growth, cells experience hypoxia. Therefore, we investigated how hypoxia modulates the levels of Spry proteins. Hypoxia elevated the levels of all four expressed Spry isoforms in HeLa cells. Amounts of endogenous Spry2 in LS147T and HEP3B cells were also elevated by hypoxia. Using Spry2 as a prototype, we demonstrate that silencing and expression of prolyl hydroxylase domain proteins (PHD1-3) increase and decrease, respectively, the cellular content of Spry2. Spry2 also preferentially interacted with PHD1-3 and von Hippel-Lindau protein (pVHL) during normoxia but not in hypoxia. Additionally, Spry2 is hydroxylated on Pro residues 18, 144, and 160, and substitution of these residues with Ala enhanced stability of Spry2 and abrogated its interactions with pVHL. Silencing of pVHL increased levels of Spry2 by decreasing its ubiquitylation and degradation and thereby augmented the ability of Spry2 to inhibit FGF-elicited activation of ERK1/2. Thus, prolyl hydroxylase mediated hydroxylation and subsequent pVHL-elicited ubiquitylation of Spry2 target it for degradation and, consequently, provide a novel mechanism of regulating growth factor signaling.
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