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Chapter 24 Insulin‐Like Growth Factor‐2/Mannose‐6 Phosphate Receptors

Authors
Publisher
Elsevier Science & Technology
Identifiers
DOI: 10.1016/s0083-6729(08)00624-9
Keywords
  • Igf Type 2 Receptor
  • Insulin Like Growth Factor
  • Mannose 6‐Phosphate
  • Lysosome
  • Transforming Growth Factor‐β
  • Proliferin
  • Leukemia Inhibitory Factor
  • Protein Trafficking
  • Fetal Growth
  • Tumor Suppressor Proteins
Disciplines
  • Biology

Abstract

Abstract 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‐β, 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.

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