Abstract
Extracellular signals that promote cell growth activate cascades of protein kinases. The kinases are dephosphorylated and deactivated by a single type-2A protein phosphatase. The catalytic subunit of type-2A protein phosphatase was phosphorylated by tyrosine-specific protein kinases. Phosphorylation was enhanced in the presence of the phosphatase inhibitor okadaic acid, consistent with an autodephosphorylation reaction. More than 90% of the activity of phosphatase 2A was lost when thioadenosine triphosphate was used to produce a thiophosphorylated protein resistant to autodephosphorylation. Phosphorylation in vitro occurred exclusively on Tyr307. Phosphorylation was catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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ErbB Receptors / physiology
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Ethers, Cyclic / pharmacology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Humans
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In Vitro Techniques
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Okadaic Acid
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Oncogene Protein pp60(v-src) / pharmacology
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Phosphoprotein Phosphatases / metabolism*
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Phosphorylation / drug effects
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Protein Phosphatase 2
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Protein-Tyrosine Kinases / physiology
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Rabbits
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Receptor, Insulin / physiology
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Thionucleotides / pharmacology
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Tyrosine / metabolism*
Substances
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Ethers, Cyclic
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Thionucleotides
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Okadaic Acid
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6-thioinosine-5'-triphosphate
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Tyrosine
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ErbB Receptors
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Protein-Tyrosine Kinases
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Receptor, Insulin
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Oncogene Protein pp60(v-src)
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Phosphoprotein Phosphatases
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Protein Phosphatase 2