Insulin receptor substrate 1 (IRS1) (IRS1)

Insulin receptor substrate 1 (IRS1) is a critical cytosolic adaptor protein that transmits signals from the insulin and insulin-like growth factor 1 (IGF-1) receptors to intracellular pathways (UniProt P35568) [1]. Upon insulin binding, the receptor phosphorylates IRS1 on tyrosine residues, creating docking sites for SH2-domain proteins like PI3K, which is essential for glucose uptake (StatPearls) [2]. Conversely, phosphorylation on specific serine residues, such as Ser307, by kinases like JNK or S6K, acts as a negative feedback mechanism that promotes insulin resistance (Copps & White, 2012) [3]. In metabolic diseases like Type 2 diabetes, the balance between tyrosine and serine phosphorylation is often disrupted. In oncology, IRS1 overactivity is associated with increased cell proliferation and survival in various cancers, including breast and prostate cancer (Mardilovich et al., 2009) [4]. While few drugs target IRS1 directly, metabolic therapies like metformin and thiazolidinediones function by indirectly improving the IRS1 phosphorylation profile to restore insulin sensitivity (PubChem) [5].

Other names

IRS-1Insulin receptor substrate-1HIRS-1Phospho-IRS1

Modulation of phosphorylation states to enhance or inhibit downstream signaling pathways like PI3K/Akt and MAPK.