The role of protein kinase C- in PTH stimulation of IGF-binding protein-5 mRNA in UMR-106–01 cells

Erclik, Mary S., and Jane Mitchell. The role of protein kinase Cin PTH stimulation of IGF-binding protein-5 mRNA in UMR-106–01 cells. Am J Physiol Endocrinol Metab 282: E534–E541, 2002; 10.1152/ajpendo.00417.2001.—We have investigated the role of protein kinase C (PKC) signal transduction pathways in parathyroid hormone (PTH) regulation of insulin-like growth factor-binding protein-5 (IGFBP-5) gene expression in the rat osteoblast-like cell line UMR-106–01. Involvement of the PKC pathway was determined by the findings that bisindolylmaleimide I inhibited 40% of the PTH effect, and 1 M bovine PTH-(3–34) stimulated a 10-fold induction of IGFBP-5 mRNA. PTH-(1–34) and PTH-(3–34) (100 nM) both stimulated PKCtranslocation from the membrane to the nuclear fraction. Rottlerin, a PKC-specific inhibitor, and a dominant negative mutant of PKCwere both able to significantly inhibit PTH-(1–34) and PTH-(3–34) induction of IGFBP-5 mRNA, suggesting a stimulatory role for PKCin the effects of PTH. Phorbol 12myristate 13-acetate (PMA) stimulated PKCtranslocation from the cytosol to the membrane and inhibited 50% of the PTH-(1–34), forskolin, and 8-bromoadenosine 3 ,5 -cyclic monophosphate-stimulated IGFBP-5 mRNA levels, suggesting that PKCnegatively regulates protein kinase A (PKA)mediated induction of IGFBP-5 mRNA. These results suggest that the induction of IGFBP-5 by PTH is both PKA and PKC dependent and PKCis the primary mediator of the effects of PTH via the PKC pathway.