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P-Type Lectins: Cation-Independent Mannose-6-Phosphate Reeptors

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Animal Lectins: Form, Function and Clinical Applications

Abstract

Insulin and the insulin-like growth factors, IGF-I (IGF1) and –II (IGF2) are structurally related peptides that elicit a large number of similar biological effects in target cells. Three well-characterized receptor complexes bind one or more of these peptides with high affinity. Two of these receptors, denoted as type 1, are ligand-activated tyrosine kinases with similar heterotetrameric α2β2 subunit structures which bind insulin or IGF-1, respectively, with highest affinity. Ligand-stimulated tyrosine autophosphorylation of these receptors further activates their intrinsic tyrosine kinase activities both in vitro and in intact cells. Rapid signal transduction follows such receptor autophosphorylation and tyrosine kinase activation, leading to increased serine phosphorylation of many cell proteins and decreased serine phosphorylation of several others. A third receptor in this group binds IGF-1 and -2, lacks kinase activity and is denoted as type II IGF receptor (IGF2R). The cell surface receptor for IGF2 also functions as a cation-independent M6PR. Therefore, cation-independent mannose 6-phosphate receptor (CI-MPR) is also referred as insulin-like growth factor 2 receptor (IGF2R) or IGF2/MPR. The CI-MPR/IGF2R is a single transmembrane domain glycoprotein that plays a major role in the trafficking of lysosomal enzymes from the trans-Golgi network (TGN) to the endosomal-lysosomal (EL) system. This CI-MPR/IGF2R has also a potential role in growth factor maturation and clearance, and mediates IGF2-activated signal transduction through a G-protein-coupled mechanism. The IGF2R/CI-MPR rapidly recycles between the cell surface membrane and intracellular membrane compartments, providing for the rapid uptake of both IGF2 and M6P-linked lysosomal enzymes. Insulin action markedly increases the proportion of receptors in the plasma membrane and the uptake of bound ligands. Embryonic development and normal growth require exquisite control of IGFs (Dahms et al. 2008; Gary-Bobo et al. 2007).

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    G. S. Gupta (Former Professor and Chairman)

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Gupta, G.S. (2012). P-Type Lectins: Cation-Independent Mannose-6-Phosphate Reeptors. In: Animal Lectins: Form, Function and Clinical Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1065-2_4

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