From the Research
Insulin interacts with tyrosine kinase by binding to the insulin receptor on cell surfaces, which activates the receptor's intrinsic tyrosine kinase activity, as demonstrated in the most recent study 1. When insulin binds to the alpha subunits of its receptor, it causes a conformational change that enables the beta subunits to autophosphorylate on specific tyrosine residues. This autophosphorylation fully activates the receptor's tyrosine kinase domain, allowing it to phosphorylate intracellular substrate proteins such as insulin receptor substrates (IRS), as shown in previous studies 2, 3. Once phosphorylated, these substrates serve as docking sites for various signaling molecules, particularly those containing SH2 domains, which initiate downstream signaling cascades. These pathways include the PI3K/Akt pathway, which mediates glucose uptake by promoting GLUT4 translocation to the cell membrane, and the Ras/MAPK pathway, which regulates cell growth and differentiation, as discussed in earlier research 4, 5. The most recent study 1 highlights a second, previously unrecognized IR signaling pathway that is intracellular domain-dependent, but ligand and tyrosine kinase-independent (LYK-I), which regulates the cellular machinery involved in senescence, matrix interaction, and response to extrinsic challenges. This receptor tyrosine kinase mechanism is fundamental to insulin's metabolic effects, including glucose uptake, glycogen synthesis, and inhibition of gluconeogenesis, and dysfunction in this signaling pathway contributes to insulin resistance and type 2 diabetes. Key aspects of insulin's interaction with tyrosine kinase include:
- Activation of the receptor's intrinsic tyrosine kinase activity upon insulin binding
- Autophosphorylation of the beta subunits on specific tyrosine residues
- Phosphorylation of intracellular substrate proteins such as IRS
- Initiation of downstream signaling cascades, including the PI3K/Akt and Ras/MAPK pathways.