Identification of determinants that confer ligand specificity on the insulin receptor.

摘要: We have previously shown, using truncated soluble recombinant receptors, that substituting the 62 N-terminal amino acids of alpha subunit from insulin-like growth factor I receptor (IGFIR) with corresponding 68 insulin (IR) results in a chimeric an approximately 200-fold increase affinity for and only 5-fold decrease (IGFI) (Kjeldsen, T., Andersen, A. S., Wiberg, F. C., Rasmussen, J. Schaffer, L., Balschmidt, P., Moller, K. B., N. P. H. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 4404-4408). demonstrate these IR also confer on intact IGFI holoreceptor both membrane-bound state when solubilized by Triton X-100. Furthermore, this domain can be subdivided into two regions (amino 1-27 28-68 subunit) that, replacing IGFIR sequences, increases chimeras 8- 20-fold, respectively, minor effects affinity. Within latter regions, we found 38-68 IR, representing 13 acid differences IGFIR, same 20-fold IGFIR. Finally, position 42 to 50 are not responsible thus propose at least determinants within involved defining ligand specificity receptor, one or combination remaining seven between 38 conferring receptor.