[The compartmentalization of the epidermal growth factor (EGF) during endocytosis in cells expressing a normal EGF receptor and one lacking the major autophosphorylation sites].
The endocytosis of 125I-EGF was studied in transfectant NIH3T3 cells expressing a normal full-length EGF receptor (HER14) and a mutant receptor lacking 4 major autophosphorylation sites by deletion of 126 amino acids from the carboxyl terminus (CD126). The rates of 125I-EGF internalization and degradation in CD 126 were found to be slightly lower compared to HER14. Analysis of 125I-EGF-complexes compartmentalization during endocytosis, made by subcellular fractionation in 17% Percoll gradient, revealed different behavior of full-length and truncated receptors. In the former case the major portion of internalized 125I-EGF was found to transit rapidly from light (early) to heavy (or late) endosomes, while in CD126 cells the efficiency of this transition, which reflects sorting of EGF-receptor complexes for degradative pathway, was significantly lower. At the same time, cells with the truncated receptor showed an increased level of 125I-EGF recycling compared to HER14. The results obtained suggest that in regulation of EGF receptor sorting for degradative pathway a protein, containing so called SH2-domain, is involved. Failure of the truncated receptor to be sorted efficiently may indicate a direct interaction of this protein with phosphorylated C-terminal tyrosines of the receptor.
Sokolova
I P
IP
Vdovina
I B
IB
Kornilova
E S
ES
Nikol'skiĭ
N N
NN
D016475:3T3 Cells; D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D010766:Phosphorylation; D014162:Transfection / Q000502:physiology
D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors