Sci. STKE, 5 February 2002
Signal Attenuation Extinguishing Signals is a Sorted Affair
Down-regulation of signals transduced by some cell surface receptors is thought to involve receptor internalization into endosomes and subsequent transport to lysosomes where they are degraded. Inward budding of endosomes results in the formation of multivesicular bodies (MVBs) that separate proteins that are recycled to the surface from those destined for the lysosome. Lloyd et al. show in Drosophila that a protein that contains a FYVE-domain called hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) regulates MVB formation and hence, sorting and degradation of the receptor tyrosine kinases Torso and the epidermal growth factor receptor. Mutant embryos showed changes in gene expression patterns that reflected prolonged receptor signaling. Endosomes in mutant cells were also enlarged because of an inability of endosomes to invaginate. The authors suggest that in addition to endosome-to-lysosome trafficking, localization of signaling receptors into endosomal MVBs is critical for promoting the degradation of activated receptors.
T. E. Lloyd, R. Atkinson, M. N. Wu, Y. Zhou, G. Pennetta, H. J. Bellen, Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell 108, 261-269 (2002). [Online Journal]
Citation: Extinguishing Signals is a Sorted Affair. Sci. STKE 2002, tw54 (2002).
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