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Studies with Insulin and Insulin-Like Growth Factor-I Show that the Increased Labeling of Phosphatidylinositol-3,4-Bisphosphate Is not Sufficient to Elicit the Diverse Actions of Epidermal Growth Factor on MA-10 Leydig Tumor Cells

The Population Council New York, New York 10021

Address requests for reprints to: Dr. Mario Ascoli, Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa 52242–1109.

Abstract

In a recent publication we showed that addition of mouse epidermal growth factor (mEGF) to MA-10 Leydig tumor cells rapidly leads to an increase in the incorporation of [³H]inositol-derived radioactivity into an unusual lipid that was identified as phosphatidylinositol-3,4-bisphosphate (PI-3,4-P₂). Other ligands that are known to bind to MA-10 cells, such as hCG and arginine vasopressin, however, did not elicit this effect. Inasmuch as mEGF modulates the differentiated functions of MA-10 cells in a number of ways, our findings raised the possibility that PI-3,4-P₂ may be an intracellular mediator of these actions of mEGF.

In an attempt to answer this question, we set out to determine if other ligands increase the labeling of PI-3,4-P₂ in MA-10 cells prelabeled with [³H]inositol, and if such ligands mimic the diverse biological actions of mEGF on these cells. The experiments presented herein show that insulin, insulin-like growth factor-I, and transforming growth factor- increase the labeling of PI-3,4-P₂ in MA-10 cells, but only transforming growth factor- mimics the actions of mEGF on the differentiated functions of MA-10 cells. We conclude that an increase in the labeling of PI-3,4-P₂ is not sufficient to elicit these actions of mEGF.

FOOTNOTES

This work was supported by a grant from the NIH (CA-40629; to M.A.).

^* Established Researcher from the National Research Council of Argentina (IBYME-CONICET), supported by a fellowship from the Andrew W. Mellon Foundation.

Received for publication January 15, 1990. Revision received February 21, 1990. Accepted for publication February 21, 1990.

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