Publications [#99269] of Gayathri R Devi

Papers Published

1. F Garmroudi, G Devi, DH Slentz, BS Schaffer, RG MacDonald, Truncated forms of the insulin-like growth factor II (IGF-II)/mannose 6-phosphate receptor encompassing the IGF-II binding site: characterization of a point mutation that abolishes IGF-II binding., Molecular endocrinology (Baltimore, Md.), vol. 10 no. 6 (June, 1996), pp. 642-51, ISSN 0888-8809
   (last updated on 2013/05/16)

   Abstract:
   Complete understanding of the functional significance of insulin-like growth factor II (IGF-II) binding by the IGF-II/mannose-6-phosphate (Man-6-P) receptor requires mapping and ultimately mutational analysis of the receptor's IGF-II binding domain. Recent advances have localized the IGF-II binding site to extracytoplasmic repeats 10-11. To improve resolution of the binding site map, a nested set of epitope-tagged, truncated forms of the human IGF-II/Man-6-P receptor were transiently expressed in COS-7 cells. The IGF-II binding properties of truncated receptors immunoprecipitated from cell lysates and conditioned media were determined by affinity cross-linking. From the largest truncated receptor, encompassing extracytoplasmic repeats 8-11 (M(r) 68 K), through the smallest, comprised primarily of repeat 11 (M(r) 23 K), all were able to bind and cross-link to IGF-II. As a group, the truncated receptors had similar affinities for IGF-II, but with relative binding affinities 5-to 10-fold lower than those of full-length receptors. A point mutation substituting threonine for isoleucine at residue 1572, located in the NH2-terminal half of repeat 11, completely abolished IGF-II binding. We conclude that repeat 11 of the IGF-II/Man-6-P receptor's extracytoplasmic domain contains the minimal elements required for binding and cross-linking to IGF-II, and that lle1572 and other residues within the NH2-terminal half of repeat 11 are particularly important for IGF-II interaction.

   Keywords:
   Animals • Binding Sites • Cross-Linking Reagents • Humans • Insulin-Like Growth Factor II • Iodine Radioisotopes • Mutation • Precipitin Tests • Receptor, IGF Type 2 • Recombinant Proteins • Repetitive Sequences, Nucleic Acid • Substrate Specificity • genetics • genetics* • metabolism • metabolism*