Tyrosine phosphorylation of the insulin receptor is not required for receptor internalization: studies in 2,4-dinitrophenol-treated cells.
The relation between insulin-stimulated autophosphorylation of the insulin receptor and internalization of the receptor was studied in Fao rat hepatoma cells. Treatment of Fao cells with 2,4-dinitrophenol for 45 min depleted cellular ATP by 80% and equally inhibited insulin-stimulated receptor autophosphorylation, as determined by immunoprecipitation of surface-iodinated or [32P]phosphate-labeled cells with anti-phosphotyrosine antibody. In contrast, internalization of the insulin receptor and internalization and degradation of 125I-labeled insulin by 2,4-dinitrophenol-treated cells were normal. These data show that autophosphorylation of the insulin receptor is not required for the receptor-mediated internalization of insulin in Fao cells and suggest that insulin receptor recycling is independent of autophosphorylation.
Backer
J M
JM
Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215.
Kahn
C R
CR
White
M F
MF
D019297:2,4-Dinitrophenol; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004140:Dinitrophenols / Q000494:pharmacology*; D007163:Immunosorbent Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008114:Liver Neoplasms, Experimental; D010766:Phosphorylation; D019000:Phosphotyrosine; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014475:Uncoupling Agents
D004140:Dinitrophenols; D007328:Insulin; D007457:Iodine Radioisotopes; D014475:Uncoupling Agents; D019000:Phosphotyrosine; D014443:Tyrosine; D000255:Adenosine Triphosphate; D011972:Receptor, Insulin; D019297:2,4-Dinitrophenol