Mechanisms of regulation of G(11)alpha protein by dexamethasone in osteoblastic UMR 106-01 cells.

Abstract

We have previously demonstrated that glucocorticoids increased G(q/11)alpha protein expression and phospholipase C activity in the rat osteosarcoma cell line UMR 106-01. In this study, we demonstrated that G(11)alpha is the primary G(q)-subtype family member expressed in UMR cells. Dexamethasone treatment increased the expression of G(11)alpha protein in both a time- and a dose-dependent manner. Glucocorticoid treatment significantly increased the half-life of G(11)alpha protein from 20.3 to 63 h. Steady-state G(11)alpha mRNA level was also increased by glucocorticoid treatment by approximately 70%. This change was not the result of changes in RNA stability but rather the result of increased transcription, because the glucocorticoid-mediated upregulation of G(11)alpha mRNA was blocked by the transcription inhibitor actinomycin D. The dexamethasone induction of G(11)alpha mRNA occurred after a time lag of 12-24 h and was blocked by the protein synthesis inhibitor cycloheximide. These results suggest that the dexamethasone-induced rise in G(11)alpha protein results primarily from changes in the degradation rate of the protein, whereas changes in G(11)alpha mRNA play a smaller role and require de novo synthesis of regulatory protein(s).