title: A PDZ domain protein interacts with the C-terminal tail of the insulin-like growth factor-1 receptor but not with the insulin receptor.
abstract: In this study, we report on the isolation of a PDZ domain protein, here designated as IIP-1, insulin-like growth factor-1 (IGF-1) receptor-interacting protein-1, which binds to the IGF-1 receptor, but not to the related insulin receptor, and which is involved in the regulation of cell motility. The interaction between the IGF-1 receptor and IIP-1 as well as a splice variant IIP-1/p26 was demonstrated in the yeast two-hybrid system. Using co-precipitation experiments, we confirmed the interaction in transfected cells as well as in vitro. Analysis of deletion mutants indicates that the PDZ domain of IIP-1 mediates interaction with the C-terminal tail of the IGF-1 receptor (serine-threonine-cysteine). This finding demonstrates that the C terminus of the IGF-1 receptor acts as novel PDZ domain binding site. Immunofluorescence analysis revealed an overlapping localization of IIP-1 and the IGF-1 receptor in the breast cancer cell line MCF-7. A functional connection between IIP-1 and the IGF-1 receptor is further supported by the finding that the level of expression of IIP-1 and the IGF-1 receptor strongly correlates in different normal and cancer cells. Furthermore, overexpression of IIP-1 resulted in an attenuation of migration of MCF-7 cells, which is one of the biological activities mediated by the IGF-1 signaling system.
authors.affiliation: Roche Diagnostics GmbH, Pharma Research, Nonnenwald 2, Penzberg 82372, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ligensa
authors.forename: S
authors.initials: S
authors.lastname: Krauss
authors.forename: D
authors.initials: D
authors.lastname: Demuth
authors.forename: R
authors.initials: R
authors.lastname: Schumacher
authors.forename: J
authors.initials: J
authors.lastname: Camonis
authors.forename: G
authors.initials: G
authors.lastname: Jaques
authors.forename: K M
authors.initials: KM
authors.lastname: Weidner
mesh_terms: D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D003001:Cloning, Molecular; D003545:Cysteine / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017526:Receptor, IGF Type 1 / Q000737:chemistry*; D011972:Receptor, Insulin / Q000737:chemistry*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013912:Threonine / Q000737:chemistry; D014162:Transfection; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D013912:Threonine; D012694:Serine; D005982:Glutathione Transferase; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D003545:Cysteine