Proteomics

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Identification and functional annotation of the Src-regulated kinome, part 2


ABSTRACT: Despite significant progress, our understanding of how specific oncogenes transform cells is still limited and likely underestimates the complexity of downstream signalling events. Herein, we describe a novel, integrated approach that addresses this knowledge gap. This utilizes mass spectrometry-based chemical proteomics to characterize the global impact of an oncogene on the expressed kinome, and then functionally annotates the regulated kinases. As an example, we identified approximately one hundred protein kinases exhibiting altered expression and/or phosphorylation in Src-transformed mammary epithelial cells. Screening with corresponding siRNAs identified nine kinases, including SGK1, as being essential for Src-induced transformation. In contrast, MAP4K5 suppressed transformation in a manner enhanced by S335 phosphorylation. In triple negative breast cancer cells, Src positively regulated SGK1 expression and combined inhibition of Src and SGK1 was more effective at inhibiting cell proliferation than either treatment alone. Therefore, this approach not only provides major mechanistic insights into oncogenic transformation but also aids the design of improved therapeutic strategies.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Hugh Ma  

LAB HEAD: Roger Daly

PROVIDER: PXD011146 | Pride | 2018-11-21

REPOSITORIES: Pride

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