Abstract
The membrane protein plasma cell differentiation antigen 1 (PC-1) has been purified as an inhibitor of insulin receptor tyrosine kinase activity and has been implicated in the pathogenesis of NIDDM. However, we show here that PC-1 is a general protein kinase inhibitor in vitro and that this inhibition results from the hydrolysis of ATP by the intrinsic nucleotide pyrophosphatase activity of PC-1. Thus, the inhibition diminished with increasing ATP concentrations, and it was nullified when the ATP concentration was kept constant with a regenerating system or when ATP was added repetitively. When care was taken to avoid ATP depletion, PC-1 did not affect the insulin sensitivity of insulin receptor autophosphorylation. We conclude that the reported inhibition of insulin signaling by PC-1 does not result from a direct inhibition of the insulin receptor kinase activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism*
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Adenosine Triphosphate / pharmacology
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Animals
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Casein Kinases
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Cattle
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Cell Membrane / metabolism
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Enzyme Inhibitors / pharmacology
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Female
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Humans
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Insulin / pharmacology*
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Kinetics
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Liver / metabolism
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Membrane Glycoproteins / isolation & purification
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Membrane Glycoproteins / pharmacology*
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Muscle, Skeletal / enzymology
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Myocardium / metabolism
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Phosphoric Diester Hydrolases*
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Phosphoric Monoester Hydrolases
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Phosphorylase Kinase / isolation & purification
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Phosphorylase Kinase / metabolism
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Placenta / metabolism
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Pregnancy
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Protein Kinases / isolation & purification
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Protein Kinases / metabolism
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Pyrophosphatases*
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Rabbits
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Rats
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Receptor, Insulin / antagonists & inhibitors*
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Receptor, Insulin / metabolism*
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Spleen / enzymology
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Swine
Substances
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Enzyme Inhibitors
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Insulin
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Membrane Glycoproteins
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Adenosine Triphosphate
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Protein Kinases
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Phosphorylase Kinase
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Receptor, Insulin
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Casein Kinases
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Phosphoric Monoester Hydrolases
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Phosphoric Diester Hydrolases
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ectonucleotide pyrophosphatase phosphodiesterase 1
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Pyrophosphatases