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 internalization and endosomal trafficking of the receptor in vivo in response to EGF. When the waved-2 mice were injected with EGF, there was approximately 50% less tyrosine phosphorylation detected in whole-liver homogenate compared to wild-type background mice. Although EGF increased the EGF receptor levels in the early and late liver endosomal fractions of waved-2 mice, its trafficking was delayed compared to wild-type mice. Ubiquitination of the EGF receptor may affect its endosomal sorting. We found that a similar amount of EGF receptor was immunoprecipitated from the endosomal fractions of EGF-treated waved-2 and wild-type with anti-ubiquitin antibody. These results demonstrate that the waved-2 EGF receptor can become ubiquitinated and can be trafficked to the late endosomes, although it appears that its kinase deficiency delays this process.
Keegan
B P
BP
Department of Physiology, State University of New York at Buffalo, Buffalo, New York, 14215, USA.
Sheflin
L G
LG
Spaulding
S W
SW
D000818:Animals; D003433:Crosses, Genetic; D011992:Endosomes / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019000:Phosphotyrosine / Q000378:metabolism; D017354:Point Mutation
D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors