[Phosphorylation of lysosomal hydrolases in human cancer and its significance].
Many lysosomal hydrolases in cases of human cancer were found to be accompanied by acidic variant forms together with the major hydrolase components. Such variants were found to be phosphorylated not only at their carbohydrate moiety which contributes largely to their acidic property, but also at the protein moiety. We identified a cAMP-dependent protein kinase which is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in transplanted lung cancer than in normal lung in the presence of cAMP. The B enzyme purified from normal human liver was found to contain 0.6mol of Pi/mol of B enzyme, and protein kinase treatment added a further 1.3mol Pi to give a single phosphopeptide (X) containing phosphothreonine. On the other hand, the B1 enzyme purified from transplanted human lung cancer which had been labeled in vivo with [32P] Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X (Thr) which is available only by deliberate phosphorylation of the native, ordinary B enzyme, appears to be cancer-associated. Increased phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease in the activity upon overphosphorylation, using an artificial substrate.
D000230:Adenocarcinoma / Q000201:enzymology*; D000818:Animals; D002803:Chondro-4-Sulfatase / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D013429:Sulfatases / Q000378:metabolism*
D011494:Protein Kinases; D006867:Hydrolases; D013429:Sulfatases; D002803:Chondro-4-Sulfatase; D005966:Glucuronidase