The mannose 6-phosphate/insulin-like growth factor II receptor, IGF-IIR (also designated M6P/IGF2R), is a ubiquitously expressed integral glycoprotein. By binding glycoproteins through two of its extracytoplasmic domains, IGF-IIR mediates the activation of TGF1 (a growth inhibitor), the degradation of IGF-II and the transport of lysosomal enzymes. Subsequently, IGF-IIR can form oligomeric complexes, which increase the affinity of IGF-IIR for lysosomal enzymes. Unlike IGF-IR, IGF-IIR does not potentiate the signaling of IGF-I or IGF-II, which have mitogenic, cell survival and insulin-like effects. Therefore, IGF-IIR is characterized as a tumor suppressor. Furthermore, the IGF-IIR gene is located on chromosome 6q26, which is commonly mutated or deleted in several human cancers.
