Regulation of phosphatidylinositol-phosphate kinase IIgamma gene transcription by thyroid-stimulating hormone in thyroid cells

Abstract

This study was performed to evaluate the effects of thyroid-stimulating hormone (TSH) on phosphatidylinositol-4-phosphate 5-kinase type IIgamma (PIPKIIgamma) gene expression in the thyrocytes of FRTL-5 cells. Although PIPKIIgamma mRNA was expressed constantly in the absence of added TSH, its expression increased remarkably in the presence of 10(-9) M TSH. This increase started within 6 h of the addition of TSH, and reached a maximum at 8 h. The mRNA expression properties of PIPKIIgamma in the cells were identified using inhibitors. Actinomycin D blocked PIPKIIgamma transcription strongly, while cycloheximide did not. In an experiment using 5,6-dichlo-1-beta-d -ribofuranosylbenzimidaxole, the half-life of PIPKIIgamma mRNA was approximately 6 h in the presence or absence of TSH, and it was not affected by the stability of the PIPKIIgamma mRNA. The effects of TSH on PIPKIIgamma gene expression were specific, and other growth factors examined (transferrin, insulin and hydrocortisone) did not alter its expression. It is possible that the mechanism of PIPKIIgamma gene expression is involved in the permissive effect of the TSH-cAMP cascade proper. Our results indicate, for the first time, that the expression of PIPKIIgamma is regulated transcriptionally by TSH in thyrocytes.

P-Rex

“…The fact that there are cytoplasmic substrates, e.g., the p38 regulated/activated kinase (PRAK) and heat shock protein 27 (Hsp27), which are phosphorylated by p38 MAPK in the cytoplasm points to the diversity of its activity for downstream targets. Interestingly, the activation of p38 MAPK by DNA-damaging agents supports the idea that the p38 MAPK cascade might be initiated in the nucleus (Suh 2001). Activation of p38 MAPK Family, Fig.…”

Park2

“…Phosphorylation may also be regulated by mitogenic cell stimulation with EGF or PDGF and to a lesser extent with lysophosphatidic acid or bradykinin (Itoh et al 1998). Enzyme expression may also be regulated in thyrocytes by thyroid-stimulating hormone (Park et al 2001).…”