Down-regulation of epidermal growth factor receptor signalling within multivesicular bodies.

Activated EGFR (epidermal growth factor receptor) undergoes ESCRT (endosomal sorting complex required for transport)-mediated sorting on to the intraluminal vesicles of MVBs (multivesicular bodies) before degradation in the lysosome. Sorting of endocytosed EGFR on to the intraluminal vesicles of MVBs removes the catalytic domain of the EGFR from the cytoplasm, resulting in termination of receptor signalling. The formation of intraluminal vesicles that contain EGFR is promoted by EGF stimulation in a mechanism that depends on the EGFR substrate, annexin 1. Signalling from endocytosed EGFR is also subject to down-regulation through receptor dephosphorylation by PTPs (protein tyrosine phosphatases), such as PTP1B, an enzyme thought to reside on the ER (endoplasmic reticulum). In the present paper, we review how the phosphorylation state of components of the MVB sorting machinery, as well as the EGFR, may play a critical role in regulating EGFR sorting and signalling.