Insulin-like growth factor-2/mannose-6 phosphate receptors. 2009

Hesham M El-Shewy, and Louis M Luttrell
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

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.

UI MeSH Term Description Entries
D007335 Insulin-Like Growth Factor II A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults. IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014644 Genetic Variation Genotypic differences observed among individuals in a population. Genetic Diversity,Variation, Genetic,Diversity, Genetic,Diversities, Genetic,Genetic Diversities,Genetic Variations,Variations, Genetic
D017527 Receptor, IGF Type 2 A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain. IGF Type 2 Receptor,IGF-II Receptor,Receptor, IGF-II,Receptor, Insulin-Like Growth Factor II,Receptor, Insulin-Like Growth Factor Type 2,Receptor, Mannose-6-Phosphate,IGF-2 Receptor,Insulin-Like-Growth-Factor II Receptor,Mannose-6-Phosphate Receptor,Receptors, IGF-2,Receptors, Insulin-Like Growth Factor II,IGF 2 Receptor,IGF II Receptor,IGF-2 Receptors,Insulin Like Growth Factor II Receptor,Mannose 6 Phosphate Receptor,Receptor, IGF II,Receptor, IGF-2,Receptor, Insulin Like Growth Factor II,Receptor, Insulin Like Growth Factor Type 2,Receptor, Insulin-Like-Growth-Factor II,Receptor, Mannose 6 Phosphate,Receptors, IGF 2,Receptors, Insulin Like Growth Factor II
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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