Effect of a major histocompatibility complex class I peptide on insulin-like growth factor-I receptor internalization and biological signaling.
Previous studies have shown that a peptide derived from the murine major histocompatibility complex class 1 (MHC-1) antigen inhibits insulin receptor internalization and enhances insulin action. Consequently, we have studied the effect of this peptide [Dk-(62-85)] derived from the MHC-1 antigen on insulin-like growth factor-I (IGF-I) internalization and action. When Chinese hamster ovary cells that overexpress human IGF-I receptors were incubated in the presence or absence of 30 microM Dk-(62-85), IGF-I internalization was inhibited by 43.9 +/- 1.7% (P < 0.005). This inhibitory effect was dose responsive, with a half-maximal effect at 8 microM and a maximal effect at 30 microM. The peptide did not affect IGF-I receptor autophosphorylation or ligand-induced phosphorylation of an endogenous substrate, pp185, in vivo. When added alone, the peptide increased glucose transport into Chinese hamster ovary cells by 66.3 +/- 16.0%, whereas when the peptide was added together with IGF-I, ligand-stimulated glucose transport was inhibited. In conclusion, 1) the MHC-1-derived peptide Dk-(62-85) inhibits IGF-I internalization in a dose-responsive fashion; 2) Dk-(62-85) does not affect receptor kinase activity, as IGF-I receptor autophosphorylation and endogenous substrate phosphorylation are unaltered; and 3) Dk-(62-85) stimulates glucose transport by itself, but inhibits IGF-I stimulated transport.
Hsu
D
D
Department of Medicine, University of California-San Diego, La Jolla 92093.
Olefsky
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003847:Deoxyglucose / Q000378:metabolism; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection
C083041:D(kappa) (62-85) peptide; D015395:Histocompatibility Antigens Class I; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D011494:Protein Kinases; D017526:Receptor, IGF Type 1