Mannose 6-phosphate/ insulin-like growth factor II receptor fails to interact with G-proteins. Analysis of mutant cytoplasmic receptor domains.
The binding of insulin-like growth factor II ( IGF II) to the mannose 6-phosphate (M6P)/IGF II receptor has previously been reported to induce the activation of trimeric G(i)2 proteins by functional coupling to a 14-amino acid region within the cytoplasmic receptor domain (Nishimoto, I., Murayama, Y., Katada, T., Ui, M., and Ogata, E. (1989) J. Biol. Chem. 264, 14029-14038). In the present study, we examined further the potential functional coupling of G-proteins with the human M6P/IGF II receptor and mutant receptors lacking the proposed G-protein activator sequence. IGF II treatment of mouse L-cells expressing either wild type or mutant M6P/ IGF II receptors failed to attenuate the pertussis toxin- catalyzed modification of a 40-kDa protein or enhance GTPase activity. In broken L-cell membranes expressing wild type or mutant M6P/ IGF II receptors, 30 nM IGF II also failed to affect the pertussis toxin substrate activity. By using phospholipid vesicles reconstituted with human wild type or mutant M6P/ IGF II receptors and pertussis toxin-sensitive G-proteins, no stimulation of GTP gamma S binding to or GTPase activity of G(i)2, G(o)1, or G(i)/G(o) mixtures were observed in response to 1 microM IGF II. Furthermore, in vesicles containing purified wild type M6P/ IGF II receptors and monomeric G alpha o1 or G alpha i2 and beta gamma dimers no effects of IGF II on GTP gamma S binding could be detected. However, when vesicles reconstituted with M6P/ IGF II receptors and G(i)2 proteins were incubated with 100 microM mastoparan GTP gamma S binding was stimulated and GTPase activity was increased significantly. These results indicate that the human M6P/IGF II receptor neither interacts with G-proteins in mouse L-cell membranes nor is coupled to G(i)2 proteins in phospholipid vesicles. This study suggests strongly that the M6P/ IGF II receptor does not function in transmembrane signaling in response to IGF II.[1]References
- Mannose 6-phosphate/insulin-like growth factor II receptor fails to interact with G-proteins. Analysis of mutant cytoplasmic receptor domains. Körner, C., Nürnberg, B., Uhde, M., Braulke, T. J. Biol. Chem. (1995) [Pubmed]
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