Abstract
A specific inhibitor of protein tyrosine phosphatase (PTPase), RK-682 (3-hexadecanoyl-5-hydroxymethyl-tetronic acid) was isolated from microbial metabolites. In vitro, RK-682 inhibited dephosphorylation activity of CD45 and VHR with IC50 54 and 2.0 microM, respectively. In situ, sodium orthovanadate and RK-682 enhanced the phosphotyrosine level of Ball-1 cells, a human B cell leukemia, but not the phosphoserine/threonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression. Sodium orthovanadate inhibited the cell cycle progression at G2/M boundary phase, on the other hand, RK-682 inhibited the G1/S transition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / metabolism
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Antifungal Agents / pharmacology
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Blotting, Western
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Cell Cycle / drug effects
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Cell Cycle Proteins / antagonists & inhibitors*
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Dual Specificity Phosphatase 3
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Enzyme Inhibitors / isolation & purification
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Enzyme Inhibitors / pharmacology*
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Ethers, Cyclic / pharmacology
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G1 Phase / drug effects*
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Humans
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Kinetics
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Leukemia, B-Cell
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Okadaic Acid
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Organophosphorus Compounds / metabolism
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Phosphoprotein Phosphatases / antagonists & inhibitors*
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Phosphoprotein Phosphatases / chemistry
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Phosphoprotein Phosphatases / isolation & purification
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Phosphoprotein Phosphatases / pharmacology
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Phosphoproteins / metabolism
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Phosphotyrosine / metabolism
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Pyrans*
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Spiro Compounds*
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Streptomyces / chemistry
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Tumor Cells, Cultured
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Vanadates / pharmacology
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cdc25 Phosphatases
Substances
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Aniline Compounds
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Antifungal Agents
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Cell Cycle Proteins
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Enzyme Inhibitors
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Ethers, Cyclic
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Organophosphorus Compounds
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Phosphoproteins
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Pyrans
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RK 682
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Spiro Compounds
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tautomycin
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Okadaic Acid
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Phosphotyrosine
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Vanadates
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4-aminophenylphosphate
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Phosphoprotein Phosphatases
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DUSP3 protein, human
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Dual Specificity Phosphatase 3
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Protein Tyrosine Phosphatases
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cdc25 Phosphatases