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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

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

The mouse insulin-like growth factor II (IGF-II) gene encodes a polypeptide that plays a role in embryonic growth. We have examined the temporal and spatial pattern of expression of this gene in sections of the mouse conceptus between embryonic days 4.0 and 8.5 by in situ hybridization. Abundant IGF-II transcripts were detected in all the trophectodermal derivatives, after implantation. Labeling was then observed in primitive endoderm, but was transient and disappeared after formation of the yolk sac. Expression was next detected in extraembryonic mesoderm at the early primitive streak stage. Labeling in the embryo proper appeared first at the late primitive streak/neural plate stage in lateral mesoderm and in anterior-proximal cells located between the visceral endoderm and the most cranial region of the embryonic ectoderm. The position of the latter cells suggests that their descendants are likely to participate in the formation of the heart and the epithelium of the ventral and lateral walls of the foregut, where intense labeling was observed at the neural fold stage. Hybridization was also detected in cranial mesenchyme, including neural crest cells. The intensity of hybridization signal increased progressively in paraxial (presomitic and somitic) mesoderm, while declining in the ectoplacental cone. The neuroectoderm and surface ectoderm did not exhibit hybridization at any stage. Immunohistochemical analysis indicated co-localization of IGF-II transcripts, translated pre-pro-IGF-II, and the cognate IGF-II/mannose-6-phosphate receptor. These correlations are consistent with the hypothesis that IGF-II has an autocrine function.
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PMID:Pattern of the insulin-like growth factor II gene expression during early mouse embryogenesis. 196 8

The insulin-like growth factor II (IGF-II) receptor is identical to the mannose-6-phosphate receptor (M-6-P), but its role as a somatomedin transducer is uncertain. IGF-II/M-6-P receptor expression was studied by in situ hybridization (ISH) in the developing rat. Expression occurs in extra-embryonic membranes at the time of IGF-II mRNA induction and later at paracrine/autocrine sites of IGF-II action (skeletal muscle and perichondrium) in the embryo. Highest levels of receptor mRNA occur in heart and major vessels. Postnatally transcription is strongly down-regulated. This suggests a role for the IGF-II/M-6-P receptor in IGF-II action or turnover during development distinct from its role in lysosomal transport.
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PMID:Expression of the IGF-II/mannose-6-phosphate receptor mRNA and protein in the developing rat. 217 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

Amino acid sequences deduced from rat complementary DNA clones encoding the insulin-like growth factor II (IGF-II) receptor closely resemble those of the bovine cation-independent mannose-6-phosphate receptor (Man-6-P receptorCI), suggesting they are identical structures. It is also shown that IGF-II receptors are adsorbed by immobilized pentamannosyl-6-phosphate and are specifically eluted with Man-6-P. Furthermore, Man-6-P specifically increases by about two times the apparent affinity of the purified rat placental receptor for 125I-labeled IGF-II. These results indicate that the type II IGF receptor contains cooperative, high-affinity binding sites for both IGF-II and Man-6-P-containing proteins.
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PMID:A single receptor binds both insulin-like growth factor II and mannose-6-phosphate. 296 83

We cloned and sequenced the 8767-bp full-length cDNA for the chicken cation-independent mannose-6-phosphate receptor (CI-MPR), of interest because, unlike its mammalian homologs, it does not bind insulin-like growth factor II (IGF-II). The cDNA encodes a protein of 2470 aa that includes a putative signal sequence, an extracytoplasmic domain consisting of 15 homologous repeat sequences, a 23-residue transmembrane sequence, and a 161-residue cytoplasmic sequence. Overall, it shows 60% sequence identity with human and bovine CI-MPR homologs, and all but two of 122 cysteine residues are conserved. However, it shows much less homology in the N-terminal signal sequence, in repeat 11, which is proposed to contain the IGF-II-binding site in mammalian CI-MPR homologs, and in the 14-aa residue segment in the cytoplasmic sequence that has been proposed to mediate G-protein-coupled signal transduction in response to IGF-II binding by the human CI-MPR. Transient expression in COS-7 cells produced a functional CI-MPR which exhibited mannose-6-phosphate-inhibitable binding and mediated endocytosis of recombinant human beta-glucuronidase. Expression of the functional chicken CI-MPR in mice lacking the mammalian CI-MPR should clarify the controversy over the physiological role of the IGF-II-binding site in mammalian CI-MPR homologs.
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PMID:Cloning and expression of the cDNA of chicken cation-independent mannose-6-phosphate receptor. 756 13

Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein concentration suggesting a renotropic function in diabetic kidney growth. In order to further examine the possible involvement of the insulin-like growth factor system in initial diabetic kidney growth, we have studied the expression of the kidney insulin-like growth factor II/mannose-6-phosphate receptor during the first 4 days after induction of diabetes in rats. Using a specific antiserum (#3637) raised against the insulin-like growth factor II/mannose-6-phosphate receptor of rat chondrosarcoma a specific band with an apparent molecular weight of 220 kDa was identified in Western blotting experiments with kidney and liver protein extracts. In untreated diabetic rats a transient increase of the kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration was measured 24-48 h after the induction of diabetes (mean increase in kidney 140% and liver 112%, n = 5). This increase was followed by a subsequent decrease in the insulin-like growth factor II/mannose-6-phosphate receptor protein concentration after 3-4 days of diabetes. Insulin treatment prevented the rise both in kidney and liver tissue. Kidney weight in untreated diabetic rats increased by 25% after 4 days. In conclusion, the present study shows a transient increase of insulin-like growth factor II/mannose-6-phosphate receptor concentration in hypertrophying diabetic kidneys and in diabetic livers, contemporarily with the previously described increase in kidney insulin-like growth factor I and insulin-like growth factor binding protein content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased kidney and liver insulin-like growth factor II/mannose-6-phosphate receptor concentration in experimental diabetes in rats. 775 75

The receptor for insulin-like growth factor type 2, also known as the cation-independent mannose-6-phosphate receptor (Igf2/Mpr), is a multifunctional receptor thought to play a role in lysosomal targeting, cell growth and signal transduction. Igf2/Mpr has been mapped to the mouse Tme locus and shown to be an imprinted gene, which further suggests a role in embryonic growth regulation. To define the functions of Igf2/Mpr, we have generated mice lacking this gene. We report here that maternal inheritance of an Igf2/Mpr null allele (-/+) as well as homozygosity for the inactive allele (-/-) is generally lethal at birth and mutants are about 30% larger, indicating that maternal expression of Igf2/Mpr is essential for late embryonic development and growth regulation. The phenotype is probably caused by an excess of Igf2 because the introduction of an Igf2 null allele rescued the Igf2/Mpr mutant mice. Mutant mice also have organ and skeletal abnormalities and missort mannose-6-phosphate-tagged proteins. A few (-/+) mice reactivated their paternal Igf2/Mpr allele in some tissues and survived to adults. But no (-/-) mice survived, indicating a role for the reactivated paternal allele in postnatal survival.
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PMID:Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. 798 40

Genetic evidence suggests that the insulin-like growth factor II (IGF-II)/mannose-6-phosphate receptor (IGF2R) slows growth. A soluble form of IGF2R (sIGF2R) is produced by proteolytic cleavage of the intact cellular receptor and is found at high levels in fetal and neonatal plasma. To test the hypothesis that sIGF2R modulates organ size in vivo, we generated transgenic mice expressing a mouse Igf2r complementary DNA in which the transmembrane domain sequence was deleted. The transgene was driven by the keratin-10 promoter and was expressed at the highest levels in the skin and alimentary canal. Transgenics showed disproportionately reduced size of the alimentary canal, where the wet weight was decreased by 9-20% and the dry weight was decreased by 20-30%, whereas the water content per unit dry weight was not significantly changed. In addition, the circulating levels of IGF-II and the latent form of transforming growth factor-beta1 were increased by 58-77% and 56-140%, respectively, whereas plasma epidermal growth factor levels showed a 24-35% reduction. The serum and tissue activities of four lysosomal enzymes were not affected, with the exception of the colon in the line expressing the transgene at highest levels, where enzyme activities were decreased compared with control values. These results support a significant role for the sIGF2R in local modulation of organ size in vivo.
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PMID:Local reduction of organ size in transgenic mice expressing a soluble insulin-like growth factor II/mannose-6-phosphate receptor. 972 44


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