Inhibition of insulin receptor phosphorylation by PC-1 is not mediated by the hydrolysis of adenosine triphosphate or the generation of adenosine
1995
Grupe, A. | Alleman, J. | Goldfine, I.D. | Sadick, M. | Stewart, T.A.
Individuals with insulin resistance show increased levels of PC-1 expression in skeletal muscle and fibroblasts, and in transfected cell lines that overexpress PC-1 there is a reduction in the insulin-stimulated insulin receptor tyrosine phosphorylation. As PC-1 is a type II transmembrane protein with extracellular phosphodiesterase and pyrophosphatase activity, increased expression of PC-1 at the cell surface will decrease extracellular adenosine triphosphate levels and increase extracellular adenosine levels. Consequently it is possible that PC-1-mediated insulin resistance could be caused either by a decrease in adenosine triphosphate or an indirect increase in adenosine levels. We have tested this hypothesis and find that the PC-1-mediated inhibition of insulin-stimulated insulin receptor autophosphorylation is not altered by agents that alter the level or action of adenosine. Further, a mutated PC-1 with a single amino acid change that abolishes the phosphodiesterase and pyrophosphatase activities is still able to inhibit insulin-stimulated insulin receptor phosphorylation. The results of these experiments indicate that the phosphodiesterase activity of PC-1 is not involved in the inhibition of insulin receptor autophosphorylation.
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