Elevated glucocorticoid receptor transactivation and down-regulation of alpha 1 integrin are associated with loss of plasma membrane Ca2+-ATPase isoform 1. Academic Article uri icon

abstract

  • We have previously shown that inhibition of expression of the plasma membrane Ca(2+)-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 Ca(2+)-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 Ca(2+)-ATPase 1 do not produce alpha(1) integrin, which is required for both collagen adherence and neurite extension. Because alpha(1) 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 Ca(2+)-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 Ca(2+)-ATPase 1 because constitutive expression of alpha(1) integrin did not restore their nerve growth factor-mediated neurite extension capability. The impact of plasma membrane Ca(2+)-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 Ca(2+)-mediated signals.

published proceedings

  • J Biol Chem

author list (cited authors)

  • Brandt, P. C., & Vanaman, T. C

citation count

  • 7

complete list of authors

  • Brandt, PC||Vanaman, TC

publication date

  • August 2000