IRS1-derived peptide

Product Name: IRS1-derived peptide

Sequence One Letter Code: KKSRGDYMTMQIG-NH2

Sequence Three Letter Code: H-Lys-Lys-Ser-Arg-Gly-Asp-Tyr-Met-Thr-Met-Gln-Ile-Gly-NH2

Chemical Formula:C63H108N20O19S2

Molecular Weight: 1513.9

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Diabetes and Metabolic Syndrome

Source / Species: Human, mouse, rat

Conjugation: Unconjugated

Code Nacres: NA.26

Application: This peptide corresponds to residues 979–989 of insulin receptor substrate-1 (IRS-1) and contains the conserved YMXM motif that mediates binding to the SH2 domains of the p85 regulatory subunit of phosphoinositide 3-kinase (PI3K). Phosphorylation of this region following insulin or IGF-1 receptor activation promotes recruitment of PI3K and triggers downstream signaling pathways that regulate metabolism, cell growth, and survival. Because of its defined interaction motif, the peptide is widely used to investigate insulin signaling and PI3K activation mechanisms. It is suitable for phosphorylation assays, protein–protein interaction studies, and inhibitor screening targeting metabolic signaling pathways. The peptide supports research into insulin resistance, diabetes, metabolic syndrome, and growth factor–mediated signal transduction.

Current Research: Introduction to IRS-1 Peptides in Metabolic Signaling Research Insulin signaling is a central pathway regulating glucose metabolism, cell growth, and survival. Disruption of this pathway is closely associated with metabolic disorders such as insulin resistance, type 2 diabetes, and metabolic syndrome. To better understand the molecular mechanisms underlying insulin signaling, researchers frequently use short synthetic peptides that reproduce critical signaling motifs from intracellular adaptor proteins. One such reagent is the IRS-1 (979–989) peptide, a sequence derived from insulin receptor substrate-1 (IRS-1). This peptide contains a conserved signaling motif that plays a crucial role in the activation of phosphoinositide 3-kinase (PI3K), making it a valuable experimental tool for studying insulin receptor signaling and downstream metabolic pathways. IRS-1 and Its Role in Insulin Receptor Signaling IRS-1 is an intracellular adaptor protein that functions as a primary signaling mediator downstream of the insulin receptor and insulin-like growth factor-1 (IGF-1) receptor. Upon stimulation by insulin or IGF-1, the receptor undergoes autophosphorylation and subsequently phosphorylates specific tyrosine residues on IRS-1. These phosphorylation events create docking sites for signaling proteins containing Src homology 2 (SH2) domains. The region spanning residues 979–989 of IRS-1 includes a conserved YMXM motif, which is one of the most important binding sequences involved in insulin signaling. Once phosphorylated, this motif serves as a recognition site for the SH2 domains of the p85 regulatory subunit of PI3K. This interaction is a key step that links receptor activation to downstream intracellular signaling cascades. Recruitment and Activation of PI3K The binding of PI3K to phosphorylated IRS-1 initiates activation of the PI3K–Akt signaling pathway, a major metabolic signaling axis. When the p85 regulatory subunit binds to phosphorylated IRS-1, it recruits the catalytic subunit of PI3K to the plasma membrane. This recruitment allows PI3K to phosphorylate phosphatidylinositol lipids, generating second messengers that activate downstream effectors. Activation of the PI3K pathway ultimately leads to the stimulation of multiple cellular responses. These include glucose uptake, glycogen synthesis, protein translation, and regulation of cell survival. Because this pathway integrates signals controlling both metabolism and cell growth, it has become a major focus in research on metabolic diseases and cancer biology. Structural Motif for Protein–Protein Interaction Studies The IRS-1 (979–989) peptide reproduces the YMXM interaction motif, allowing researchers to examine the molecular details of PI3K recruitment and SH2-domain binding. Synthetic peptides containing this motif can be phosphorylated or modified to mimic the activated state of IRS-1, enabling precise analysis of signaling interactions. Because the peptide represents a well-defined binding sequence, it is commonly used in protein–protein interaction studies. Researchers can use the peptide to evaluate how SH2-containing proteins recognize phosphorylated tyrosine motifs and to characterize the binding affinity between IRS-1 and the p85 subunit of PI3K. These interaction studies are essential for understanding how signaling specificity is achieved in insulin receptor pathways and how alterations in these interactions may contribute to metabolic dysfunction. Applications in Phosphorylation and Kinase Assays The IRS-1 peptide is also widely used in phosphorylation assays designed to examine kinase activity associated with insulin and growth factor signaling. By providing a defined substrate sequence, the peptide allows researchers to study how kinases modify tyrosine residues and how phosphorylation regulates downstream signaling events. In biochemical experiments, phosphorylated forms of the peptide can serve as probes for SH2 domain recognition, while non-phosphorylated forms can be used to investigate kinase-mediated phosphorylation reactions. This flexibility makes the peptide suitable for a variety of assay formats, including enzymatic activity assays and fluorescence-based binding studies. Utility in Inhibitor Screening and Drug Discovery The IRS-1 (979–989) peptide is particularly useful in inhibitor screening assays targeting components of the insulin signaling pathway. Because the peptide directly participates in PI3K recruitment, it provides a convenient platform for identifying molecules that disrupt this interaction. Compounds that interfere with the phosphorylation of IRS-1 or with SH2-domain binding can be evaluated using peptide-based assays. These experiments are valuable for discovering new modulators of PI3K signaling, which may have therapeutic potential in metabolic diseases or cancer. High-throughput assay formats incorporating this peptide enable rapid evaluation of compound libraries, helping accelerate the development of drugs targeting metabolic signaling networks. Supporting Research in Metabolic Disease and Signal Transduction Synthetic peptides representing key signaling motifs provide researchers with powerful tools for dissecting complex cellular pathways. The IRS-1 (979–989) peptide supports studies investigating the molecular mechanisms underlying insulin resistance, diabetes, and metabolic syndrome. By enabling precise analysis of PI3K recruitment and activation, it helps clarify how metabolic signals are transmitted within cells. In addition, the peptide is useful for examining broader growth factor–mediated signaling pathways, since similar SH2-domain interactions are involved in multiple receptor tyrosine kinase systems. Insights gained from these studies contribute to a better understanding of metabolic regulation, cellular growth control, and disease-related signaling alterations. Conclusion The IRS-1 (979–989) peptide containing the conserved YMXM motif is an important research tool for investigating insulin receptor signaling and PI3K activation. Its ability to reproduce a critical interaction site within IRS-1 makes it highly suitable for phosphorylation assays, protein–protein interaction studies, and inhibitor screening applications. By enabling detailed analysis of the molecular events that regulate metabolic signaling pathways, this peptide supports research into insulin resistance, diabetes, metabolic syndrome, and growth factor–dependent signal transduction. As metabolic disease research continues to expand, reagents that model key signaling motifs remain essential for advancing our understanding of cellular regulation.