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Comparison of known EGF receptor and ErbB3 down-regulation pathways. EGF stimulation causes recruitment of cbl to the EGF receptor. Tyrosine phosphorylation of cbl then promotes receptor ubiquitination and trafficking to the lysosome. In contrast, NRG1 stimulates the PI3K/Akt pathway, resulting in USP8 stabilization through the phosphorylation of T907. USP8 in turn stabilizes Nrdp1, which ubiquitinates ErbB3 to promote its degradation.
