The internalization and endosomal trafficking of the EGF receptor in response to EGF is delayed in the waved-2 mouse liver

The EGF receptor in waved-2 mice contains a point mutation that renders it kinase deficient. We investigated how the waved-2 mutation affects the inte rnalization and endosomal trafficking of the receptor in vivo in response t o EGF. When the waved-a mice mere injected with EGF, there was similar to 5 0% less tyrosine phosphorylation detected in whole-liver homogenate compare d to wild-type background mice. Although EGF increased the EGF receptor lev els in the early and late liver endosomal fractions of waved-a mice, its tr afficking was delayed compared to wild-type mice. Ubiquitination of the EGF receptor may affect its endosomal sorting. We found that a similar amount of ECF receptor was immunoprecipitated from the endosomal fractions of EGF- treated waved-a and wild-type with antiubiquitin antibody. These results de monstrate that the waved-2 EGF receptor can become ubiquitinated and can be trafficked to the late endosomes, although it appears that its kinase defi ciency delays this process. (C) 2000 Academic Press.