Protein kinase C activation and phosphate uptake are altered in intact mucolipidosis type-4 skin fibroblasts.
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.
Department of Paediatrics, Hadassah University Hospital, Mt. Scopus, Jerusalem, Israel.
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Turgeman
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Boneh
D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009081:Mucolipidoses / Q000201:enzymology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012867:Skin / Q000201:enzymology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010710:Phosphates; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate