Research ArticleCell Biology

Regulation of Epidermal Growth Factor Receptor Trafficking by Lysine Deacetylase HDAC6

Sci. Signal.  22 Dec 2009:
Vol. 2, Issue 102, pp. ra84
DOI: 10.1126/scisignal.2000576

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Setting a Speed Limit on EGFR Traffic

Receptor tyrosine kinases interact with ligands at the cell surface to trigger intracellular signaling cascades. In some cases, these receptors are internalized, a process that can either enable them to initiate signaling cascades from intracellular membranes or target them for lysosomal degradation. Lissanu Deribe et al. connect acetylation of the microtubule cytoskeleton to regulation of delivery of epidermal growth factor receptors (EGFRs) to lysosomes. HDAC6, a cytoplasmic lysine deacetylase, was identified as binding to the inactive EGFR, stimulating deacetylation of α-tubulin, and decreasing the rate of delivery of EGFR from the early endosome to late endosomes or lysosomes. Phosphorylation of HDAC6, which decreased its activity, by activated EGFR created a negative feedback loop, leading to increased degradation of activated EGFRs.