Phosphotyrosine-Dependent Interaction of SHC and Insulin Receptor Substrate 1 with the NPEY Motif of the Insulin Receptor via a Novel Non-SH2 Domain

• DOI: 10.1128/mcb.15.5.2500
• Publication Date: 2015-10-09T00:16:07Z
• Authors: Thomas A. Gustafson; Weimin He; Ann Craparo; Charles D. Schaub; Thomas J. O'Neill
• Keywords: Insulin receptor substrate; Phosphotyrosine-binding domain; IRS1; IRS2

The SHC proteins have been implicated in insulin receptor (IR) signaling. In this study, we used the sensitive two-hybrid assay of protein-protein interaction to demonstrate that interacts directly with IR. is mediated by amino acids 1 238 and therefore independent Src homology 2 domain. dependent upon IR autophosphorylation, since eliminated mutation ATP-binding site. addition, mutational analysis Asn-Pro-Glu-Tyr (NPEY) motif within juxtamembrane domain showed importance Asn, Pro, Tyr residues both substrate (IRS-1) binding. We conclude phosphorylation Tyr-960 necessary for efficient interaction. This highly reminiscent IRS-1 IR, show IR-binding can substitute yeast COS cells. identify a homologous region domains IRS-1, which term SAIN (SHC NPXY-binding) domain, may explain basis these interactions. appears represent novel able interact autophosphorylated receptors such as