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AGO2 phosphorylation by c-Src kinase promotes tumorigenesis.

ABSTRACT: Numerous studies have reported that c-Src is highly expressed with high tyrosine kinase activity in a variety of tumors. However, it remains unclear whether c-Src contributes to the miRNA pathway. Here, we report that c-Src can interact with and phosphorylate AGO2, a core component of RISC complex, at tyr 393, tyr 529 and tyr749. Mechanistically, it is confirmed that c-Src phosphorylation of AGO2 at tyr393 reduces its binding to DICER, thereby suppressing the maturation of long-loop pre-miR-192. However, the other two phosphorylation sites don't work on this function. Significantly, Ectopic expression of wild-type AGO2, but not the three tyrosine site mutants, has an obvious tumor-promoting effect in vitro and in vivo, which function could be blocked thoroughly by treatment with c-Src kinase inhibitor, Saracatinib. Our findings identify AGO2 as c-Src target and c-Src phosphorylation of AGO2 may therefore play a potential role during tumor progress.

SUBMITTER: Liu T

PROVIDER: S-EPMC6992904 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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AGO2 phosphorylation by c-Src kinase promotes tumorigenesis.

Liu Tianqi T Zhang Hailong H Fang Jiayu J Yang Zhi Z Chen Ran R Wang Yanli Y Zhao Xian X Ge Shengfang S Yu Jianxiu J Huang Jian J

Neoplasia (New York, N.Y.) 20200122 3

Numerous studies have reported that c-Src is highly expressed with high tyrosine kinase activity in a variety of tumors. However, it remains unclear whether c-Src contributes to the miRNA pathway. Here, we report that c-Src can interact with and phosphorylate AGO2, a core component of RISC complex, at tyr 393, tyr 529 and tyr749. Mechanistically, it is confirmed that c-Src phosphorylation of AGO2 at tyr393 reduces its binding to DICER, thereby suppressing the maturation of long-loop pre-miR-192. ...[more]

PMID: 31981897

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