Insulin receptor and Insulin-like growth factor 2 receptor (INSR/IGF2R)

The entry "INSR and IGF2 receptor" refers to two distinct proteins: the Insulin Receptor (INSR) and the Insulin-like Growth Factor 2 Receptor (IGF2R). INSR is a transmembrane receptor tyrosine kinase that plays a central role in regulating glucose homeostasis and lipid metabolism upon binding insulin or IGF-2 (specifically the IR-A isoform) (UniProt: P06213). In contrast, IGF2R, also known as the cation-independent mannose-6-phosphate receptor, primarily functions as a "decoy" or clearance receptor that sequesters IGF-2, preventing it from activating growth-promoting signaling through INSR or IGF1R (UniProt: P11717). While INSR is a primary therapeutic target for diabetes and certain cancers, IGF2R is often viewed as a tumor suppressor due to its role in limiting IGF-2 bioavailability and is also utilized for the lysosomal delivery of enzyme replacement therapies like Cerliponase alfa (PubMed: 21170082). Combining these into a single target designation is non-standard as they possess different structural architectures, signaling mechanisms, and pharmacological profiles.

Other names

Insulin receptorIRCD220Insulin-like growth factor 2 receptorIGF2RM6PRCD222Cation-independent mannose-6-phosphate receptorCI-MPR

Insulin receptor (INSR) agonists activate the PI3K/AKT and MAPK pathways via tyrosine phosphorylation to regulate glucose uptake and cell growth (UniProt: P06213). The Insulin-like growth factor 2 receptor (IGF2R) primarily acts as a clearance receptor that sequesters IGF-2 for lysosomal degradation and serves as a transporter for mannose-6-phosphate (M6P) tagged enzymes (UniProt: P11717).