Journal of Biological Chemistry
Volume 275, Issue 32, 11 August 2000, Pages 24534-24539
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MECHANISMS OF SIGNAL TRANSDUCTION
Elevated Glucocorticoid Receptor Transactivation and Down-regulation of α1 Integrin Are Associated with Loss of Plasma Membrane Ca2+-ATPase Isoform 1*

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We have previously shown that inhibition of expression of the plasma membrane Ca2+-ATPase isoform 1 in PC6 cells leads to loss of nerve growth factor-mediated neurite extension (Brandt, P. C., Sisken, J. E., Neve, R. L., and Vanaman, T. C. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 13843–13848). Cells lacking plasma membrane Ca2+-ATPase 1 did not attach to collagen-coated plates as tightly as controls, suggesting that a defect in adhesion might be underlying the inability to extend neurites. We report here that cell lines lacking plasma membrane Ca2+-ATPase 1 do not produce α1 integrin, which is required for both collagen adherence and neurite extension. Because α1 integrin gene transcription can be down-regulated by glucocorticoids, the response of cells to glucocorticoids was investigated. Cortisol-dependent transactivation from the mouse mammary tumor virus promoter in cells lacking plasma membrane Ca2+-ATPase 1 was stimulated 145–216-fold over untreated cells compared with 15–26-fold for controls. This increase was not due to increased binding affinity of the receptor for cortisol, an increased number of cortisol-binding sites, or increased translocation of the receptor to the nucleus. Expression of additional glucocorticoid receptor-dependent genes required for neurite extension must also be altered in cells missing the plasma membrane Ca2+-ATPase 1 because constitutive expression of α1 integrin did not restore their nerve growth factor-mediated neurite extension capability. The impact of plasma membrane Ca2+-ATPase isoform 1 on other signaling systems and the resultant profound yet subtle effects on PC6 cells strongly suggests that it plays an important role in modulating signal transduction pathways downstream of Ca2+-mediated signals.

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Published, JBC Papers in Press, May 25, 2000, DOI 10.1074/jbc.M003388200

*

This work was supported by National Science Foundation Grant IBN-9604729 (to P. C. B) and National Institutes of Health Grant NS21868 (to T. C. V.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.