Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present studies, we investigated the activity of tyrosylprotein sulfotransferase (TPST) in the Golgi apparatus of PC12 cells and the regulation of this enzyme by 2-chloroadenosine, an adenosine receptor agonist. Studies employing continuous sucrose gradient and trypsinization of the membranes demonstrate that TPST is located on the luminal side of Golgi apparatus in PC12 cells. Treatment of PC12 cells with 2-chloroadenosine results in a dose-dependent decrease of TPST activity which is observable as early as 3 h after initiation of treatment, maximizes at 24-48 h with continuous exposure, and is readily reversible upon removal of the drug. While forskolin, an agent that directly increases intracellular cAMP, has no effect on TPST activity, 2-chloroadenosine equally suppressed the enzyme activity in both the wild type and a protein kinase A-deficient mutant strain of PC12 cells, indicating that such regulation of TPST activity by 2-chloroadenosine was independent of cAMP-dependent protein phosphorylation. This effect of 2-chloroadenosine can be potentiated by an adenosine uptake blocker dipyridamole but cannot be elicited by other adenosine A1 or A2 receptor agonists, further suggesting that TPST activity in PC12 cells is regulated by 2-chloroadenosine via a novel membrane receptor. Incubation of the cells with cyclo heximide, a protein synthesis inhibitor, also led to a time- and dose-dependent suppression of TPST activity. At concentrations of cycloheximide that produced maximal inhibition (approximately 50%), cotreatment with 2-chloroadenosine did not lead to a further decrease of the TPST activity. These results suggest that the sensitivity of TPST activity to be controlled by protein synthesis provides a mechanism for regulation of its activity by 2-chloroadenosine.
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PMID:2-Chloroadenosine decreases tyrosylprotein sulfotransferase activity in the Golgi apparatus in PC12 cells. Evidence for a novel receptor. 165 Mar 60

The O-sulfation of specific proteins on tyrosine residues was studied using the rat pheochromocytoma cell line PC12 as a model system. In intact PC12 cells labeled with inorganic [35S]sulfate, the major protein substrates for sulfation on tyrosine were four acidic polypeptides with apparent molecular weights of 113,000, 105,000, 86,000, and 84,000 designated as p113, p105, p86, and p84. After labeling of intact PC12 cells with inorganic [32P]phosphate, these four proteins were also found to be phosphorylated at serine residues. Peptide mapping after limited proteolysis indicated sequence homologies between p113 and p105, and between p86 and p84. In lysed PC12 cells, p113, p105, p86, and p84 were phosphorylated at serine residues by an endogenous protein kinase using [32P] ATP. Moreover, in the cell-free preparation, an enzymatic activity was detected that was able to catalyze the sulfation of the four proteins on tyrosine residues. This sulfation reaction, which used adenosine 3'-phosphate 5'-phospho[35S]sulfate as the sulfate donor, occurred in a particulate fraction of PC12 cells and was inhibited by 5 mM EDTA. These results demonstrate the presence in PC12 cells of a novel enzyme, designated here as a tyrosylprotein sulfotransferase, and imply a role for this enzyme in the post-translational processing of specific PC12 cell proteins.
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PMID:Tyrosine-O-sulfated proteins of PC12 pheochromocytoma cells and their sulfation by a tyrosylprotein sulfotransferase. 657 5