Phosphorylation of human lysosomal arylsulfatase B by cAMP-dependent protein kinase. Different sites of phosphorylation between normal and cancer tissues.
We previously demonstrated that an acidic variant (B1) of lysosomal arylsulfatase B from transplanted human lung cancer is phosphorylated on its protein and carbohydrate moieties (Gasa, S., and Makita, A. (1983) J. Biol. Chem. 258, 5034-5039). The present study identifies that a cAMP-dependent protein kinase is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in the transplanted lung cancer than in normal lung in the presence of cAMP. B enzyme purified from normal human liver was found to contain 0.6 mol/mol B enzyme, and protein kinase treatment added further 1.3 mol of Pi to give a single phosphopeptide (X). On the other hand, B1 enzyme purified from the transplanted human lung cancer which had been labeled in vivo with 32Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from normal liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X which was available only by deliberate phosphorylation of the native, ordinary B enzyme appears to be cancer-associated. Increasing phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease of the activity upon overphosphorylation, using an artificial substrate.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001665:Binding Sites; D002803:Chondro-4-Sulfatase / Q000276:immunology / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007526:Isoelectric Point; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013429:Sulfatases / Q000378:metabolism*
D000906:Antibodies; D000939:Epitopes; D010710:Phosphates; D000242:Cyclic AMP; D011494:Protein Kinases; D013429:Sulfatases; D002803:Chondro-4-Sulfatase