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

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

Wild-type and mutant human transferrin receptors (TR) have been expressed in chicken embryo fibroblasts using a helper-independent retroviral vector. By functional studies of the mutant TRs, we have identified the tetrapeptide sequence, YXRF, in the cytoplasmic tail of the receptor as the internalization signal required for high efficiency endocytosis and shown that transplanted internalization signals from the low density lipoprotein receptor (LDLR) and the cation-independent mannose-6-phosphate receptor (Man-6-PR) are able to promote rapid internalization of the human TR. A six-residue LDLR signal, FDNPVY, is required for activity in TR, whereas a four-residue Man-6-PR signal, YSKV, is sufficient. These data indicate that internalization signals are interchangeable self-determined structural motifs and that signals from type I membrane proteins are active in a type II receptor. Putative internalization signals in the cytoplasmic tails of other receptors and membrane proteins can be identified based on the sequence patterns of the LDLR, Man-6-PR, and TR signals. Two such putative four-residue internalization signals, one from the poly-Ig receptor and one from the asialoglycoprotein receptor, were tested for activity by transplantation into TR and were found to promote high efficiency internalization. These results suggest that an exposed tight turn is the conformational motif for high efficiency endocytosis.
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PMID:Structural requirements for high efficiency endocytosis of the human transferrin receptor. 143 81

MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis. We report here on MacMARCKS, a MARCKS homolog, whose synthesis is dramatically increased in macrophages when these cells are exposed to bacterial lipopolysaccharide. We have purified rabbit MacMARCKS and cloned its cDNA from rabbit and mouse. The effector domains of MacMARCKS and MARCKS are nearly identical, and both proteins bind calmodulin in a phosphorylation-regulated manner. MacMARCKS and MARCKS also share a second, highly conserved region also found in the internalization domain of the mannose-6-phosphate receptor. Our data suggest the existence of a family of PKC substrates that are targeted to different subcellular locations and that function to integrate PKC and calcium/calmodulin-dependent signals in the control of the plastic actin cytoskeleton.
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PMID:MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates. 151 35

Defensins, small cationic polypeptides with antimicrobial and cytotoxic properties, are among the principal constituents of cytoplasmic granules of mammalian neutrophils and certain macrophages. To identify conserved structural features of defensin precursors that may be important for their targeting to cytoplasmic granules or for prevention of autocytotoxicity, we isolated and sequenced three neutrophil-specific rabbit defensin cDNAs that code for preproprotein precursors to the mature defensins NP-3a, NP-4, and NP-5. The preprodefensins NP-3a, NP-4, and NP-5, like the previously characterized preprodefensins, lack consensus sequences for N-linked glycosylation, suggesting that defensins are targeted to lysosome-like granules by a mechanism not dependent on the mannose-6-phosphate receptor. Analysis of all seven known myeloid prodefensins revealed a structure wherein an anionic propiece neutralizes the cationicity of the mature peptide. Because defensins apparently require cationic epitopes for cell membrane permeabilization and cytotoxicity, charge neutralization of mature peptides by their anionic propieces may prevent autocytotoxicity during defensin synthesis and processing.
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PMID:Cationic defensins arise from charge-neutralized propeptides: a mechanism for avoiding leukocyte autocytotoxicity? 161 98

Somatomedins or insulin-like growth factors (IGFs) are two polypeptides (IGF I and IGF II) whose structure shows great homology with proinsulin. Mostly synthetized by the liver but also by many tissues, they circulate in blood bound to specific binding proteins (IGFBPs). IGFBP3, a 120 to 150 kDa complex, carries over 95% of blood IGFs and its production is stimulated by growth hormone (hGH). On the contrary, IGFBP1, a 40 to 50 kDa protein, increases in case of hGH-deficiency. An IGFBP of 34 kDa, which is the major BP in cerebrospinal fluid but also present in blood, shows a great affinity for IGF II whereas the others BPs show similar affinities for both IGFs. Little is known about the other BP, IGFBP2. Two receptors can be found in most tissues: type 1, which binds IGFs and insulin, type 2, which binds IGF II preferentially to IGF I but not insulin. Type 1 IGF receptor has structural and enzymatic (phosphorylation of one of its own sub-units) similarities with the insulin receptor and mediates the action of IGF I. Type 2 receptor has an homology with the bovine cation-dependent mannose-6-phosphate receptor and has no known function. Liver production of IGF I is mainly under the control of hGH and other factors such as diet; other tissues are less or not at all under the control of hGH. The blood levels of IGF I raise from birth to the end of puberty, then decrease and remain almost stable during adulthood. The activity of IGF I on skeletal growth is well established and the determination of its plasma levels by radioimmunoassay is of great clinical utility in the diagnosis of growth disorders. IGF I levels in blood are high in case of acromegaly, low in hGH-deficiency, undernutrition, hypothyroidy and renal failure. IGF I acts in an autocrine/paracrine way and probably endocrine sometimes. How IGF II synthesis is regulated is not well known, in any case, IGF II has no effect on growth and the regulation of its secretion is hardly influenced by hGH, its blood levels remain unchanged in acromegaly and are irregularly diminished in hGH-deficiency. Moreover, IGF I and II promote cellular growth and differentiation. This activity could be of great importance during fetal life.
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PMID:[Somatomedins]. 164 11

The internalization signals of several constitutively recycling receptors have recently been identified as regions of four or six amino acids that include an aromatic residue, usually tyrosine. Here, we show that transplanted signals from the low density lipoprotein receptor (LDLR) and cation-independent mannose-6-phosphate receptor (Man-6-PR) promote rapid internalization of the transferrin receptor (TR), directly establishing that recognition signals are interchangeable, self-determined structural motifs and that signals from type I membrane proteins are active in a type II receptor. We also show that the chemical and spatial patterns of critical residues in both four- and six-residue internalization motifs are consistent with a tight turn structure. A six-residue LDLR signal is needed for activity in TR, suggesting that an amino-terminal aromatic side chain is obligatory. In contrast, the carboxy-terminal aromatic side chain in the TR signal can be replaced by a large hydrophobic residue. Thus, internalization signals apparently require an aromatic amino-terminal residue and either an aromatic or large hydrophobic carboxy-terminal residue rather than a conserved tyrosine per se. Consistent with this conclusion, predicted internalization signals from the poly-Ig receptor, YSAF, and asialoglycoprotein receptor (ASGPR) subunit H1, YQDL, also promote internalization of TR.
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PMID:Transplanted LDL and mannose-6-phosphate receptor internalization signals promote high-efficiency endocytosis of the transferrin receptor. 165 15

Brefeldin A (BFA) is a fungal metabolite that causes a redistribution of the stacked cisternae of the Golgi complex into the endoplasmic reticulum by inhibiting anterograde transport. We report that BFA also causes membrane tubules derived from the trans-Golgi network (TGN) to fuse with early endosomes. In the presence of BFA, a mannose-6-phosphate receptor (M6PR)-enriched tubular network rapidly forms from the TGN, not from the prelysosomal compartment, and can be labeled with endocytic tracers after only 5 min of uptake at either 20 degrees C or 37 degrees C, indicating that it is also functionally an early endosome. Formation of the TGN-early endosome network is microtubule dependent and may involve modification of membrane processes affected by microtubule-associated motor activity. Concomitant with the formation of the fused TGN-early endosome network, there is a greater than 5-fold increase in cell surface M6PRs. The data suggest that BFA has revealed a membrane transport cycle between the TGN and early endosomes, perhaps used for the secretion or delivery of molecules to the cell surface.
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PMID:Brefeldin A causes a microtubule-mediated fusion of the trans-Golgi network and early endosomes. 165

Recent studies have established that in mammalian cells insulin-like growth factor-II can couple the large mannose-6-phosphate receptor to a GTP-binding protein and that the insulin-like growth factor-II-induced activation of the GTP-binding protein is inhibited by mannose-6-phosphate and lysosomal enzymes. In mouse, the gene for the large mannose-6-phosphate receptor is maternally imprinted.
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PMID:Molecular recognition and targeting of lysosomal proteins. 166 72

By using an organ culture technique, corneal endothelial cells in human embryonic eyes could be stimulated to initiate DNA synthesis by exposure to insulin like growth factor II (IGF-II). The thymidine-labelling index doubled after IGF-II supplementation. However, this stimulatory effect was neither augmented nor abrogated by the simultaneous addition of Mannose-6-Phosphate. Nor did Mannose-6-phosphate stimulate DNA synthesis in the absence of IGF II. In contrast, the IGF II effect was partly counteracted by addition of an antibody that blocks binding to the IGF type I receptor. Taken together, this data suggests that IGF II stimulates DNA-synthesis in corneal endothelium by binding to the IGF type I rather than the IGF type II/ mannose-6-phosphate receptor.
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PMID:Stimulatory effect of insulin like growth factor II on DNA synthesis in the human embryonic cornea. 166 38

The phosphorylated monosaccharide, mannose-6-phosphate (M6P), causes a dose-dependent stimulation of alkaline phosphatase production by osteoblasts. The concentrations tested ranged from 0.1 to 30 mM. A maximal effect was reproducibly seen at 10-30 mM, and represented a 30% stimulation over control cells. Glucose-6-phosphate and fructose-1-phosphate also stimulated osteoblast alkaline phosphatase production, but not to the same extent as M6P. Sugar residues such as mannose, mannose-1-phosphate, and fructose-6-phosphate had no effect. The stimulatory effect of M6P is similar to that seen with insulin-like growth factor II(IGF-II). However, increasing doses of IGF-II did not further stimulate or add to the effect of 10 mM M6P. These data indicate that the mechanism for the transduction of the stimulatory signal may be similar for both IGF-II and M6P. They do not address, however, the possibility of separate or similar binding sites for the two agents. A specific polyclonal antibody to the IGF-II/cation-independent mannose-6-phosphate receptor (IGF-II/CI-MPR) elicits the same effects as M6P and IGF-II in these bone cells. Non-immune serum used as a control does not have any effect. These results suggest that activation of the osteoblast IGF-II/CI-MPR by either M6P or a specific antibody can evoke a biological response similar to that observed with IGF-II.
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PMID:Activation of osteoblast insulin-like growth factor-II/cation-independent mannose-6-phosphate receptors by specific phosphorylated sugars and antibodies induce insulin-like growth factor-II effects. 166 83


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