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Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present evidence that insulin-like growth factor II (IGF-II) mediates growth in early mouse embryos and forms a pathway in which imprinted genes influence development during preimplantation stages. mRNA and protein for IGF-II were expressed in preimplantation mouse embryos, but the related factors IGF-I and insulin were not. IGF-I and insulin receptors and the IGF-II/mannose-6-phosphate receptor were expressed. Exogenous IGF-II or IGF-I increased the cell number in cultured blastocysts, but a mutant form of IGF-II that strongly binds only the IGF-II receptor did not. Reduction of IGF-II expression by antisense IGF-II oligonucleotides decreased the rate of progression to the blastocyst stage and decreased the cell number in blastocysts. Preimplantation parthenogenetic mouse embryos expressed mRNA for the IGF-II receptor but not for either IGF-II ligand or the IGF-I receptor, indicating that the latter genes are not expressed when inherited maternally. These data imply that some growth factors and receptors, regulated by genomic imprinting, may control cell proliferation from the earliest stages of embryonic development.
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PMID:Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. 131 21

After 3 or 4 weeks of age, insulin-like growth factor-II (IGF-II) gene expression in normal rats has been detected only in mesenchymal tissue associated with the central nervous system. In contrast, the IGF-II/mannose-6-phosphate receptor has been reported to be widely distributed in adult rat brain. This study was performed in order to clarify the cellular localization of IGF-II and IGF-II/mannose-6-phosphate receptor in rat brain by comparing an immunocytochemical map with the distribution of mRNAs by in situ hybridization. The highest levels of IGF-II mRNA were detected in the choroid plexus and meningeal membranes. In contrast, IGF-II receptor transcripts were mainly present in neuron-rich areas such as the hippocampus, with a lower signal present in the choroid plexus and meninges. Specific IGF-II receptor immunoreactivity was present in neurons throughout the forebrain, with the highest intensity in the pyramidal cell and polymorphic layers of the hippocampus and the granule cell layer of the dentate gyrus. This distribution was similar to that obtained with the in situ hybridization technique. No glial staining was detected. Although the role of IGF-II in the adult rat brain, acting through its specific receptor, is not clear; in vitro and in vivo data suggest a possible neurotropic and/or neuromodulatory action.
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PMID:Expression of insulin-like growth factor-II (IGF-II) and IGF-II/mannose-6-phosphate receptor in the rat hippocampus: an in situ hybridization and immunocytochemical study. 139 8

The primary structure of human insulin-like growth factor II receptor, predicted from the complementary DNA sequence, reveals a transmembrane receptor molecule with a large extracellular domain made up of fifteen repeat sequences and a small region homologous to the collagen-binding domain of fibronectin. The structural and biochemical features of the IGF-II receptor appear identical to those of the cation-independent mannose-6-phosphate receptor.
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PMID:Insulin-like growth factor II receptor as a multifunctional binding protein. 295 98

Recently, the sequence of the human receptor for insulin-like growth factor II (IGF-II) was found to be 80% identical [Morgan et al., (1987) Nature 329, 301-307] to the sequence of a partial clone of the bovine cation-independent mannose-6-phosphate receptor [Lobel et al., (1987) Proc. Natl. Acad. Sci. USA 84, 2233-2237]. In the present study, the purified receptor for insulin-like growth factor II (IGF-II) was found to react with two different polyclonal antibodies to the purified mannose-6-phosphate receptor. Moreover, mannose-6-phosphate was found to stimulate the binding of labeled IGF-II to the IGF-II receptor by two-fold. This effect had the same specificity and affinity as the reported binding of mannose-6-phosphate to its receptor; mannose-1-phosphate and mannose had no effect on the binding of labeled IGF-II to its receptor, and the half-maximally effective concentration of mannose-6-phosphate was 0.3 mM. Also, mannose-6-phosphate did not affect labeled IGF-II binding to the insulin receptor. These results support the hypothesis that a single protein of Mr-250,000 binds both IGF-II and mannose-6-phosphate. Furthermore, they indicate that mannose-6-phosphate can modulate the interaction of IGF-II to its receptor.
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PMID:Interactions of the receptor for insulin-like growth factor II with mannose-6-phosphate and antibodies to the mannose-6-phosphate receptor. 296 76

Seminal plasma derived factors are implicated in mediating inflammation in the female reproductive tract following insemination at mating. During inflammation, leukocytes are activated to express adhesion receptors resulting in adherence to each other and for the ECM as well as for various cell types. The present study describes the purification of a leukocyte cell-cell adhesion regulator derived from seminal vesicle fluid. Seminal vesicle fluid proteins were chromatographed by cation exchange, hydrophobic interaction and reversed phase. Chromatography on Phenyl Superose resolved two distinct forms of cell-cell adhesion regulation, type I and II. Reversed phase chromatography of fractions inducing type I adhesion resulted in the isolation of a 15kDa adhesion inducing protein (pAIF-1). The N-terminal sequence contained a hydrophobic consensus sequence which exists in: two bovine seminal vesicle proteins (BSPA3, PDC 109); IGF-II receptor; fibronectin; and the cation independent mannose-6-phosphate receptor.
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PMID:Purification of a cell-cell adhesion regulator from porcine seminal vesicle fluid. 780 52

46-kDa mannose-6-phosphate receptor forms homooligomers in cell membranes and in detergent solution. The quaternary structure of detergent-solubilized 46-kDa mannose 6-phosphate receptor is regulated by the presence of ligands, pH and receptor concentration [Waheed, A. & von Figura, K. (1990) Eur. J. Biochem. 193, 47-54). To find out whether the intracellular recycling of 46-kDa mannose 6-phosphate receptor is accompanied by changes in its quaternary structure, we have performed chemical cross-linking in membranes of intact cells. In all conditions tested, the dimer was the predominating form (more than 67% of total 46-kDa mannose 6-phosphate receptor). The amount of trimeric and tetrameric forms varied among cell lines and contributed up to 20% of total endogenous 46-kDa mannose 6-phosphate receptor in human and mouse fibroblasts. Within a given cell line, the ratio of the oligomers was not significantly changed upon elevating endosomal pH by bafilomycin A1, upon changes in receptor occupancy (treatment of cells with tunicamycin or use of mouse fibroblasts deficient in 300-kDa mannose 6-phosphate receptor), nor upon depletion of adaptors from clathrin-coated vesicles of the trans Golgi network by brefeldin A. At the cell surface, where 46-kDa mannose 6-phosphate receptor does not bind ligands, the percentage of dimer was similar to that observed intracellularly. Thus, the oligomeric state of 46-kDa mannose 6-phosphate receptor apparently does not change during recycling as well as binding and dissociation of ligands. In view of the abundance of the dimer of 46-kDa mannose 6-phosphate receptor in situ, our data suggest that it represents the main physiologically active form of the receptor, and therefore present indirect evidence that binding of ligands to 46-kDa mannose 6-phosphate receptor is probably regulated by conformational changes of receptor or ligand rather than by changes in the quaternary structure.
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PMID:The oligomeric state of 46-kDa mannose 6-phosphate receptor does not change upon intracellular recycling and binding of ligands. 864 29

Insulin-like growth factor II (IGF-II) has been implicated in the differentiation of skeletal muscle cells. In this study the putative role of IGF-II in epithelial cell differentiation was investigated. The expression of IGF-II, IGF-I receptor and IGF-II/mannose-6-phosphate receptor (IGF-II/M6P receptor) mRNA during spontaneous differentiation of the colon carcinoma cell line Caco-2 was measured. In addition, differentiation of Caco-2 cells during the cell culture period (days 1-21 in culture) was studied in parallel using morphological (light and scanning electron microscopy) and biochemical markers of growth (DNA, RNA and protein content, and beta-actin mRNA and glyceraldehyde phosphate dehydrogenase mRNA expression) and differentiation (alkaline phosphatase activity, carcinoembryonic antigen content). A putative correlation between the markers of growth and differentiation and IGF gene expression was studied using linear regression analysis. Expression of IGF-II mRNA and IGF-II/M6P receptor mRNA correlated significantly with the progress of differentiation, while the IGF-I receptor was stably expressed throughout the culture period and exhibited a crucial role for the survival of Caco-2 cells, as shown by blocking experiments employing the monoclonal anti-IGF-I receptor antibody alpha-IR3. We hypothesize that: IGF-II mRNA and IGF-II/M6P receptor mRNA are expressed in a coordinate fashion during the differentiation of Caco-2 cells; coordinate expression of IGF-II and of IGF-II/M6P receptor mRNA might point to a role for IGF-II as a growth stimulant and for the IGF-II/M6P receptor for a regulator of IGF-II bioavailability in differentiating cells; alternatively, high IGF-II/M6P receptor mRNA and protein expression in differentiated cells but low IGF-II binding to the IGF-II/M6P receptor point to an important intracellular role of this receptor type in differentiated colon epithelial cells; the IGF-I receptor mRNA is stably expressed during the differentiation process of Caco-2 cells; the IGF-I receptor protein seems to be a prerequisite for the survival of Caco-2 cells.
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PMID:Coordinate expression of insulin-like growth factor II (IGF-II) and IGF-II/mannose-6-phosphate receptor mRNA and stable expression of IGF-I receptor mRNA during differentiation of human colon carcinoma cells (Caco-2). 876 74

Recycling of mannose 6-phosphate receptors was investigated by microinjection of F(ab) fragments against their carboxy-terminal peptides (residues 54-67 or 150-164 of the cytoplasmic domain of 46 kDa and 300 kDa mannose 6-phosphate receptor, respectively). For each receptor, masking the carboxy-terminal peptide by the corresponding F(ab) fragments resulted in complete depletion of the intracellular pool. Redistributed 300 kDa mannose 6-phosphate receptor was shown to accumulate at the plasma membrane and to internalize anti-ectodomain antibodies. Internalization of anti-ectodomain antibodies was also observed for redistributed 46 kDa mannose 6-phosphate receptor. Semiquantitative analysis suggested that for both redistributed receptors the amount of intracellularly accumulated anti-ectodomain antibodies was reduced. In addition, downstream transport along the endosomal pathway was slowed down. These data suggest that sorting information for early steps in the endocytic pathway is contained within the carboxy-terminal peptides of mannose 6-phosphate receptors.
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PMID:The carboxy-terminal peptides of 46 kDa and 300 kDa mannose 6-phosphate receptors share partial sequence homology and contain information for sorting in the early endosomal pathway. 915 28

Hereditary hemochromatosis is most frequently associated with mutations in HFE, which encodes a class Ib histocompatibility protein. HFE binds to the transferrin receptor-1 (TfR1) in competition with iron-loaded transferrin (Fe-Tf). HFE is released from TfR1 by increasing concentrations of Fe-Tf, and free HFE may then regulate iron homeostasis by binding other ligands. To search for new HFE ligands we expressed recombinant forms of HFE in the human cell line 293T. HFE protein was purified, biotinylated and made into fluorescently labelled tetramers. HFE tetramers bound to TfR1 in competition with Tf, but in addition we detected a binding activity on some cell types that was not blocked by Fe-Tf or by mutations in HFE that prevent binding to TfR1. We identified this second HFE ligand as the cation independent mannose-6-phosphate receptor (CI-MPR, also known as the insulin-like growth factor-2 receptor, IGF2R). HFE:CI-MPR binding was mediated through phosphorylated mannose residues on HFE. Recombinant murine Hfe also bound to CI-MPR. HFE bound to TfR1 was prevented from binding CI-MPR until released by increasing concentrations of Fe-Tf, a feature consistent with an iron sensing mechanism. However, it remains to be determined whether endogenous HFE in vivo also acquires the mannose-6 phosphate modification and binds to CI-MPR.
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PMID:In vitro binding of HFE to the cation-independent mannose-6 phosphate receptor. 1948 39

It is well established that many cognate basolateral plasma membrane proteins are expressed apically in proximal tubule cells thus optimizing the reabsorption capacity of the kidney. The protein clathrin and its adapter proteins normally regulate basolateral polarity. Here we tested whether the unique proximal tubule polarity is dependent on an epithelial-specific basolateral clathrin adapter, AP1B, present in most other epithelia. Quantitative PCR of isolated mouse renal tubules showed that AP1B was absent in proximal tubules but present in medullary and cortical thick ascending limbs of Henle, and cortical collecting ducts. Western blot confirmed the absence of AP1B in three established proximal tubule cell lines. Knockdown of AP1B by shRNA in prototypical distal tubule MDCK cells resulted in redistribution of the basolateral parathyroid hormone receptor, the insulin-like growth factor II receptor/calcium-independent mannose-6-phosphate receptor, and the junctional adhesion molecule, JAM-C, to a proximal tubule-like nonpolar localization. Yeast two-hybrid assays detected direct interactions between the cytoplasmic tails of these plasma membrane proteins and the cargo-binding region of the AP1B complex. Hence, our results show that differential expression of AP1B contributes to normal kidney function and illustrates possible roles of this adapter protein in kidney development, physiology, and pathology.
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PMID:The absence of a clathrin adapter confers unique polarity essential to proximal tubule function. 2053 53


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