Insulin Receptor (1142-1153), pTyr1146

Product Name: Insulin Receptor (1142-1153), pTyr1146

Sequence One Letter Code: TRDI-pY-ETDYYRK

Sequence Three Letter Code: H-Thr-Arg-Asp-Ile-pTyr-Glu-Thr-Asp-Tyr-Tyr-Arg-Lys-OH

Chemical Formula:C72H108N19O27P

Molecular Weight: 1702.8

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Diabetes and Metabolic Syndrome

Source / Species: Human, zebrafish, drosophila, mouse, rat, bovine

Conjugation: Unconjugated

Code Nacres: NA.26

Application: Insulin Receptor (1142–1153), pTyr1146 is a synthetic phosphopeptide corresponding to residues 1142–1153 of the human insulin receptor β-subunit, incorporating a phosphorylated tyrosine at position 1146 within the activation loop of the receptor’s tyrosine kinase domain. Phosphorylation at Tyr1146 is a pivotal event in insulin receptor activation, promoting conformational rearrangement, enhanced catalytic activity, and recruitment of downstream signaling adaptors such as IRS proteins. As a functionally defined motif, this peptide is widely used as a substrate or reference standard in insulin receptor kinase assays and phosphotyrosine-dependent signaling studies. It supports biochemical characterization of autophosphorylation mechanisms, validation of kinase assay platforms, and screening of small-molecule or peptide-based inhibitors targeting insulin signaling. The peptide is particularly relevant for investigations into insulin resistance, metabolic syndrome, and diabetes-related signal transduction pathways.

Current Research: Phosphorylation of Tyr1146 within the activation loop of the insulin receptor (IR) kinase domain remains a central focus of metabolic signaling research. Together with Tyr1150 and Tyr1151, Tyr1146 forms part of the tri-tyrosine regulatory cluster that governs insulin receptor catalytic activation. Structural and biochemical studies demonstrate that phosphorylation at Tyr1146 stabilizes the active conformation of the kinase domain, facilitating substrate access and ATP coordination. This event is essential for efficient recruitment and phosphorylation of insulin receptor substrates (IRS proteins), thereby propagating downstream PI3K–AKT and MAPK signaling cascades. Recent research continues to dissect the sequential autophosphorylation mechanism of the insulin receptor. Evidence suggests that phosphorylation within the activation loop occurs in a stepwise manner, with Tyr1146 playing a key role in relieving autoinhibitory constraints. Time-resolved kinase assays and phospho-specific mass spectrometry analyses increasingly rely on defined phosphopeptides such as IR (1142–1153), pTyr1146 to calibrate site-specific detection and quantify kinase activity under controlled conditions. These approaches are particularly valuable in distinguishing differential phosphorylation patterns observed in insulin-sensitive versus insulin-resistant states. In the context of metabolic disease, impaired activation loop phosphorylation has been linked to insulin resistance in adipose tissue, skeletal muscle, and liver. Studies in type 2 diabetes models demonstrate reduced insulin-stimulated IR autophosphorylation, leading to attenuated IRS recruitment and diminished AKT activation. Synthetic phosphopeptides corresponding to specific activation loop residues are widely used to evaluate kinase competency, assess receptor mutations, and characterize signaling defects associated with metabolic syndrome. They also serve as standardized reagents in comparative studies examining how lipotoxicity, chronic inflammation, and oxidative stress alter proximal insulin signaling events. Another expanding area of investigation involves the development of small-molecule modulators and peptide-based inhibitors targeting insulin receptor signaling. While therapeutic strategies often aim to enhance insulin sensitivity, selective attenuation of IR signaling is being explored in oncology, where hyperactivation of insulin and IGF-1 receptors contributes to tumor proliferation. The pTyr1146-containing peptide provides a structurally defined motif for screening compounds that interact with the activation loop or modulate kinase conformation. It is also used in competitive binding assays to profile SH2 domain–containing adaptor proteins that recognize phosphotyrosine motifs. Advances in structural biology and computational modeling further underscore the relevance of activation loop phosphopeptides. Molecular dynamics simulations and crystallographic analyses frequently incorporate short phosphorylated sequences to model conformational transitions of the kinase domain. These studies help clarify how individual tyrosine residues contribute to catalytic efficiency and substrate specificity. The IR (1142–1153), pTyr1146 peptide is therefore valuable not only in enzymatic assays but also in mechanistic investigations of kinase activation dynamics. In addition, quantitative phosphoproteomics workflows increasingly require well-characterized phosphopeptide standards for method validation. Site-specific peptides corresponding to regulatory phosphorylation sites enable benchmarking of antibody specificity, optimization of LC–MS/MS parameters, and development of targeted proteomic assays. Given the clinical importance of insulin signaling biomarkers, reproducible reference materials are essential for translational research bridging basic signaling biology and metabolic disease diagnostics. Collectively, current research highlights Tyr1146 phosphorylation as a critical regulatory node in insulin receptor activation, metabolic homeostasis, and disease-associated signaling dysregulation. As a defined activation loop phosphomotif, Insulin Receptor (1142–1153), pTyr1146 remains an important tool for elucidating kinase mechanisms, validating analytical platforms, and supporting therapeutic discovery efforts in diabetes and related metabolic disorders.