title: Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system.
abstract: Using the yeast two-hybrid system, a genetic assay for studying protein-protein interactions, we have examined and compared the interaction of the insulin-like growth factor-I receptor (IGF-IR) and the insulin receptor (IR) with their two known substrates p52Shc and the insulin receptor substrate-1 (IRS-1). We also mapped the specific domains of the IGF-IR and p52Shc participating in these interactions. Our findings can be summarized as follows: (i) the tyrosine kinase activity of the IGF-IR is essential for the interaction with p52Shc and IRS-1, (ii) p52Shc and IRS-1 bind to the IGF-IR in the NPEY-juxtamembrane motif, (iii) contrary to p52Shc, IRS-1 binds also to the major autophosphorylation sites (Tyr-1131, -1135, and -1136) of the IGF-IR, and (iv) the amino-terminal domain of p52Shc is required for its association with the IR and the IGF-IR. We propose that (i) the IGF-IR and the IR share at least in part the same molecular mechanism underlying their interplay with their two substrates, p52Shc and IRS-1, and (ii) IRS-1 interacts with the IGF-IR in a fashion that is different from that used by p52Shc. Finally, our data highlight the crucial role of the juxtamembrane domain in signaling by both the IR and the IGF-IR.
authors.affiliation: INSERM U145, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Tartare-Deckert
authors.forename: D
authors.initials: D
authors.lastname: Sawka-Verhelle
authors.forename: J
authors.initials: J
authors.lastname: Murdaca
authors.forename: E
authors.initials: E
authors.lastname: Van Obberghen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D055504:Insulin Receptor Substrate Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D012697:Serine Endopeptidases; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000099160:LexA Repressor Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D011506:Proteins; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D055765:Shc Signaling Adaptor Proteins; D000099160:LexA Repressor Protein