Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucolipidosis type 4 (ML-4) is an autosomal recessive inborn error of metabolism, the pathogenesis of which is not known. We characterized protein kinase C (PKC) activation and cellular phosphate uptake in intact quiescent ML-4 skin fibroblasts and after stimulation with phorbol myristate acetate (PMA). [3H]Phorbol dibutyrate uptake was not altered in ML-4 compared to control cells. Translocation of PKC from the cytosolic to the membranous compartment upon stimulation with PMA was perturbed in ML-4 cells. Phosphate uptake was reduced in both cytosolic and membranous fractions of quiescent ML-4 cells. Stimulation with PMA did not elicit an increase in phosphate uptake in the cytosolic fraction of ML-4 cells compared with control cells, but led to comparable phosphate uptake in the membranous fraction of both cell types. The data indicate that PKC-mediated signal transduction may be perturbed in ML-4. Other kinases and phosphatases may be involved. These alterations may play an important role in the pathogenesis of this disorder.
Biochem Mol Med 1996 Oct
PMID:Protein kinase C activation and phosphate uptake are altered in intact mucolipidosis type-4 skin fibroblasts. 890 91

Mucolipidoses II and III (ML II and ML III) are lysosomal disorders in which the mannose 6-phosphate recognition marker is absent from lysosomal hydrolases and other glycoproteins due to mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Both disorders are caused by the same gene, but ML II represents the more severe phenotype. Bone manifestations of ML II include hip dysplasia, scoliosis, rickets and osteogenesis imperfecta. In this study, we sought to determine whether a recombinant adeno-associated viral vector (AAV2/8-GNPTAB) could confer high and prolonged gene expression of GNPTAB and thereby influence the pathology in the cartilage and bone tissue of a GNPTAB knock out (KO) mouse model. The results demonstrated significant increases in bone mineral density and content in AAV2/8-GNPTAB-treated as compared to non-treated KO mice. We also showed that IL-6 (interleukin-6) expression in articular cartilage was reduced in AAV2/8-GNPTAB treated ML II mice. Together, these data suggest that AAV-mediated expression of GNPTAB in ML II mice can attenuate bone loss via inhibition of IL-6 production. This study emphasizes the value of the MLII KO mouse to recapitulate the clinical manifestations of the disease and highlights its amenability to therapy.
Mol Genet Metab 2016 Apr
PMID:AAV8-mediated expression of N-acetylglucosamine-1-phosphate transferase attenuates bone loss in a mouse model of mucolipidosis II. 2685 95