Distinctive regulation of the functional linkage between the human cation-independent mannose 6-phosphate receptor and GTP-binding proteins by insulin-like growth factor II and mannose 6-phosphate
| Autor: | Yoshitake Murayama, Tetsuji Okamoto, W S Sly, Toshiaki Katada, Etsuro Ogata, J H Grubb, Ikuo Nishimoto, M Ui, T. Iiri, Tomoichiro Asano |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
GTP'
G protein Mannose Receptors Cell Surface GTPase Mannose 6-phosphate Biology Transfection Models Biological Biochemistry Receptor IGF Type 2 Mice chemistry.chemical_compound L Cells GTP-binding protein regulators GTP-Binding Proteins Insulin-Like Growth Factor II Animals Humans Molecular Biology Glucuronidase G alpha subunit Mannosephosphates Cell Membrane Cell Biology Recombinant Proteins Kinetics chemistry Guanosine 5'-O-(3-Thiotriphosphate) Signal transduction Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 265:17456-17462 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(18)38185-7 |
| Popis: | The rat insulin-like growth factor II (IGF-II) receptor develops transmembrane signaling functions by directly coupling to a guanine nucleotide-binding protein (G protein) having a 40-kDa alpha subunit, Gi-2, whereas recent studies have indicated that the IGF-II receptor is a molecule identical to the cation-independent mannose 6-phosphate receptor (CI-MPR), a receptor implicated in lysosomal enzyme sorting. In this study, by using vesicles reconstituted with the clonal human CI-MPR and G proteins, we indicated that the CI-MPR could stimulate guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) binding and GTPase activities of Gi proteins in response to IGF-II. The stimulatory effect of IGF-II on Gi-2 depended on the reconstituted amount of the CI-MPR; it could not be found in vesicles reconstituted with Gi-2 alone; and it was also observed on Gi-1 reconstituted with the CI-MPR in phospholipid vesicles. Of interest, such stimulatory effect was not reproduced by Man-6-P in CI-MPR vesicles reconstituted with either G protein. Furthermore, the affinity for Man-6-P-mediated beta-glucuronidase binding to several kinds of native cell membranes was not reduced by 100 microM GTP gamma S. Instead, however, Man-6-P dose-dependently inhibited IGF-II-induced Gi-2 activation with an IC50 of 6 microM in vesicles reconstituted with the CI-MPR and Gi-2. The action of 100 nM IGF-II was completely abolished by 1 mM Man-6-P. Such an inhibitory effect of Man-6-P was reproduced by 4000 times lower concentrations of beta-glucuronidase or similar concentrations of fructose 1-phosphate, but not by mannose or glucose 6-phosphate. These results indicate that the human CI-MPR has two distinct signaling functions that positively or negatively regulate the activity of Gi-2 in response to the binding of IGF-II or Man-6-P. |
| Databáze: | OpenAIRE |
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