Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Menkes disease is a fatal neurodegenerative disorder of childhood due to the absence or dysfunction of a putative copper-transporting P-type ATPase encoded on the X chromosome. To elucidate the biosynthesis and subcellular localization of this protein, polyclonal antisera were generated against a bacterial fusion protein encoding the 4th to 6th copper-binding domains in the amino terminus of the human Menkes protein. RNA blot analysis revealed abundant Menkes gene expression in several cell lines, and immunoblotting studies utilizing this antiserum readily detected a 178-kDa protein in lysates from these cells. Pulse-chase studies indicate that this protein is synthesized as a single-chain polypeptide which is modified by N-linked glycosylation to a mature endoglycosidase H-resistant form. Sucrose gradient fractionation of HeLa cell lysates followed by immunoblotting of individual fractions with antibodies to proteins of known intracellular location identified the Menkes ATPase in fractions similar to those containing the cation-independent mannose-6-phosphate receptor. Consistent with this observation, confocal immunofluorescence studies of these same cells localized this protein to the trans-Golgi network and a vesicular compartment with no expression in the nucleus or on the plasma membrane. Taken together, these data provide a unique model of copper transport into the secretory pathway of mammalian cells which is compatible with clinical observations in affected patients and with recent data on homologous proteins identified in prokaryotes and yeast.
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PMID:Biochemical characterization and intracellular localization of the Menkes disease protein. 894 55