The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes
Open accessAbstract
Secretion of RNAs in extracellular vesicles is a newly recognized form of intercellular communication. A potential regulatory protein for microRNA (miRNA) secretion is the critical RNA-induced silencing complex (RISC) component Argonaute 2 (Ago2). Here, we use isogenic colon cancer cell lines to show that overactivity of KRAS due to mutation inhibits localization of Ago2 to multivesicular endosomes (MVEs) and decreases Ago2 secretion in exosomes. Mechanistically, inhibition of mitogen-activated protein kinase kinases (MEKs) I and II, but not Akt, reverses the effect of the activating KRAS mutation and leads to increased Ago2-MVE association and increased exosomal secretion of Ago2. Analysis of cells expressing mutant Ago2 constructs revealed that phosphorylation of Ago2 on serine 387 prevents Ago2-MVE interactions and reduces Ago2 secretion into exosomes. Furthermore, regulation of Ago2 exosomal sorting controls the levels of three candidate miRNAs in exosomes. These data identify a key regulatory signaling event that controls Ago2 secretion in exosomes.
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Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834
Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids
Théry, C., Amigorena, S., Raposo, G., & Clayton, A. (2006) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0322s30 · Cited by 5,766
Cited by
Théry, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin‐Smith, G. K., et al. (2018) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2018.1535750 · Cited by 11,099
Self-citationShedding light on the cell biology of extracellular vesicles
van Niel, G., D'Angelo, G., & Raposo, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.125 · Cited by 8,369
Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrügger, U., et al. (2024) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12404 · Cited by 4,663
Pegtel, D. M., & Gould, S. J. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-013118-111902 · Cited by 2,682
Current knowledge on exosome biogenesis and release
Hessvik, N. P., & Llorente, A. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2595-9 · Cited by 2,362
Metadata
- Authors
- McKenzie, A. J., Hoshino, D., Hong, N. H., Cha, D. J., Franklin, J. L., Coffey, R. J., Patton, J. G., & Weaver, A. M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 15
- Issue
- 5
- Pages
- 978-987
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2340514456
- Cited by
- 423
- References
- 2
- FWCI
- 16.10
- Type
- journal article
- Language
- en
- Open access
- gold
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