ArticleThe Journal of biological chemistry2016
Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Plasma membrane transbilayer asymmetry of PI(4,5)PNature communications · 2025Article
- FGF2 is secreted in extracellular vesicles from lung cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space.eLife · 2024Article
- Cholesterol promotes clustering of PI(4,5)P2 driving unconventional secretion of FGF2.The Journal of cell biology · 2022Article
- Article
- A Role for Liquid-Ordered Plasma Membrane Nanodomains Coordinating the Unconventional Secretory Pathway of Fibroblast Growth Factor 2?Frontiers in cell and developmental biology · 2022Review
- Mechanisms of secretion and spreading of pathological tau protein.Cellular and molecular life sciences : CMLS · 2020Review
- The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)PCommunications biology · 2020Article
- Spotlight on the Transglutaminase 2-Heparan Sulfate Interaction.Medical sciences (Basel, Switzerland) · 2019Review
- Review
- Conventional and unconventional secretory proteins expressed with silkworm bombyxin signal peptide display functional fidelity.Scientific reports · 2017Article
- Key steps in unconventional secretion of fibroblast growth factor 2 reconstituted with purified components.eLife · 2017Article
- Unconventional Pathways of Secretion Contribute to Inflammation.International journal of molecular sciences · 2017Review
- Fibroblast growth factor 2.Differentiation; research in biological diversityReview
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor 2 (FGF2) is a potent mitogen promoting both tumor cell survival and tumor-induced angiogenesis. It is secreted by an unconventional secretory mechanism that is based upon direct translocation across the plasma membrane. Key steps of this process are (i) phosphoinositide-dependent membrane recruitment, (ii) FGF2 oligomerization and membrane pore formation, and (iii) extracellular trapping mediated by membrane-proximal heparan sulfate proteoglycans. Efficient secretion of FGF2 is supported by Tec kinase that stimulates membrane pore formation based upon tyrosine phosphorylation of FGF2. Here, we report the biochemical characterization of the direct interaction between FGF2 and Tec kinase as well as the identification of small molecules that inhibit (i) the interaction of FGF2 with Tec, (ii) tyrosine phosphorylation of FGF2 mediated by Tec in vitro and in a cellular context, and (iii) unconventional secretion of FGF2 from cells. We further demonstrate the specificity of these inhibitors for FGF2 because tyrosine phosphorylation of a different substrate of Tec is unaffected in their presence. Building on previous evidence using RNA interference, the identified compounds corroborate the role of Tec kinase in unconventional secretion of FGF2. In addition, they are valuable lead compounds with great potential for drug development aiming at the inhibition of FGF2-dependent tumor growth and metastasis.
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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.