Elevated glucocorticoid receptor transactivation and down-regulation of alpha(1) integrin are associated with loss of plasma membrane Ca2+-ATPase isoform 1
Pc. Brandt et Tc. Vanaman, Elevated glucocorticoid receptor transactivation and down-regulation of alpha(1) integrin are associated with loss of plasma membrane Ca2+-ATPase isoform 1, J BIOL CHEM, 275(32), 2000, pp. 24534-24539
We have previously shown that inhibition of expression of the plasma membra
ne Ca2+-ATPase isoform I 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 pl
ates 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 alpha(1) integrin, wh
ich is required for both collagen adherence and neurite extension. Because
alpha(1) integrin gene transcription can be down-regulated by glucocorticoi
ds, the response of cells to glucocorticoids was investigated. Cortisol-dep
endent transactivation from the mouse mammary tumor virus promoter in cells
lacking plasma membrane Ca2+-ATPase 1 was stimulated 145-216-fold over unt
reated cells compared with 15-26-fold for controls. This increase was not d
ue to increased binding affinity of the receptor for cortisol, an increased
number of cortisol-binding sites, or increased translocation of the recept
or to the nucleus, Expression of additional glucocorticoid receptor-depende
nt genes required for neurite extension must also be altered in cells missi
ng the plasma membrane Ca2+-ATPase 1 because constitutive expression of alp
ha(1) integrin did not restore their nerve growth factor-mediated neurite e
xtension capability. The impact of plasma membrane Ca2+-ATPase isoform 1 on
other signaling systems and the resultant profound yet subtle effects on P
C6 cells strongly suggests that it plays an important role in modulating si
gnal transduction pathways downstream of Ca2+-mediated signals.