Research ArticleCell Biology

AKT Facilitates EGFR Trafficking and Degradation by Phosphorylating and Activating PIKfyve

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Science Signaling  11 Jun 2013:
Vol. 6, Issue 279, pp. ra45
DOI: 10.1126/scisignal.2004015

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Promoting One’s Own Demise

Mutations in the genes encoding epidermal growth factor receptors (EGFRs) are linked to various cancers in humans. Understanding how signaling through EGFRs and related receptors is terminated can provide potential therapeutic targets. Ligand binding to EGFRs leads to the activation of the kinase AKT, and Er et al. found that AKT phosphorylated and activated the kinase PIKfyve, which is involved in vesicle trafficking. PIKfyve enhanced the degradation of EGFR, and inhibition of AKT resulted in an increase in EGFR abundance and downstream signaling. Thus, EGFR activity stimulates a pathway that brings about termination of its signaling.

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