Insulin-like growth factor-2/mannose-6 phosphate receptors.
The insulin-like growth factor type 2/mannose-6-phosphate (IGF-2/M6P) receptor is a multifunctional single transmembrane glycoprotein that is known to regulate diverse biological functions. It is composed of a large extracytoplasmic domain, a single transmembrane region and a short cytoplasmic tail that lacks intrinsic catalytic activity. The receptor cycles continuously between intracellular compartments and the plasma membrane, and at steady state is predominantly localized in the trans-Golgi network and endosomal compartments, and to a lesser extent on the cell surface. The receptor binds IGF-2 with higher affinity than IGF-1 and does not bind insulin. It interacts, via distinct sites, with lysosomal enzymes and a variety of other M6P-containing ligands. IGF-2/M6P receptors perform diverse cellular functions related to lysosome biogenesis and the regulation of growth and development. It regulates extracellular IGF-2 concentrations, modulating signaling through the growth-stimulatory IGF-1 receptor pathway. It appears to mediate the uptake and processing of M6P-containing cytokines and peptide hormones, such as transforming growth factor-beta, leukemia inhibitory factor, and proliferin. Some data suggest that the IGF-2/M6P receptor also functions in signal transduction by transactivating G protein-coupled sphingosine 1-phosphate receptors. Genetic evidence clearly supports a role for IGF-2/M6P receptors in organ development and growth, and recent data indicate that it may play an important role in tumor progression.
El-Shewy
Hesham M
HM
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Luttrell
Louis M
LM
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D014644:Genetic Variation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000378:metabolism*
D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II