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Cited by 423

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 access
McKenzie, Andrew J., Hoshino, Daisuke, Hong, Nan Hyung, Cha, Diana J., Franklin, Jeffrey L., Coffey, Robert J., Patton, James G., Weaver, Alissa M.·2016·Cell Reports

Abstract

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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Crossref · 10.1016/j.celrep.2016.03.085

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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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