Internalization and degradation of insulin by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells.
Chinese hamster ovary cell lines expressing either the wild-type human insulin receptor or a hybrid molecule in which the tyrosine kinase domain of the insulin receptor is replaced with that of the oncogene, v-ros were examined for their ability to internalize and degrade insulin. Cells expressing the hybrid receptor were found to internalize and degrade insulin at approximately half the rate of cells expressing the native insulin receptor. Moreover, insulin was incapable of inducing the internalization of the cell-surface hybrid molecule. In contrast, the constitutive rate of receptor internalization was found to be the same for the hybrid and wild-type receptors. These results obtained were similar to those with cells expressing either wild-type or mutant receptors lacking kinase activity. In conclusion, the substitution of the specificity of tyrosine kinase of the insulin receptor with that of the v-ros oncogene product results in defective internalization and degradation of insulin, and loss of ligand-induced receptor internalization.
Hari
J
J
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yokono
K
K
Yonezawa
K
K
Roth
R A
RA
Baba
S
S
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D007163:Immunosorbent Techniques; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection
D007328:Insulin; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin; C058682:v-ros protein, Avian sarcoma virus UR2