INSULIN-RECEPTOR AUTOPHOSPHORYLATION SITES TYROSINE-1162 AND TYROSINE-1163 CONTROL BOTH INSULIN-DEPENDENT AND INSULIN-INDEPENDENT RECEPTOR INTERNALIZATION PATHWAYS
C. Reynet et al., INSULIN-RECEPTOR AUTOPHOSPHORYLATION SITES TYROSINE-1162 AND TYROSINE-1163 CONTROL BOTH INSULIN-DEPENDENT AND INSULIN-INDEPENDENT RECEPTOR INTERNALIZATION PATHWAYS, Cellular signalling, 6(1), 1994, pp. 35
We previously reported that Chinese hamster ovary (CHO) cell lines ove
rexpressing mutated human insulin receptors (hIRs) in which the tyrosi
ne residues 1162 and 1163 were replaced by phenylalanines (CHO-Y2) exh
ibited a marked defect in hormone-induced receptor internalization as
compared to CHO transfectants overexpressing wild-type hIRs (CHO-R). T
hese two cell lines are now used to compare the role of tyrosines 1162
-1163 in basal and ligand-stimulated receptor internalization as well
as in receptor turnover. We show here that (1) in CHO-Y2 cells, basal
endocytosis, like insulin-induced internalization, was markedly altere
d despite normal receptor turnover and (2) in both CHO-R and CHO-Y2 ce
lls, basal receptor endocytosis was altered by tunicamycin, an inhibit
or of protein N-glycosylation, whereas insulin-induced internalization
was not. These results support a role for tyrosines 1162-1163 of the
IR beta subunit major autophosphorylation domain in both basal and lig
and-stimulated receptor endocytosis and provide evidence that the two
processes follow distinct pathways.