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

被引:23
作者
Erclik, MS [1 ]
Mitchell, J [1 ]
机构
[1] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2002年 / 282卷 / 03期
关键词
insulin-like growth factor-binding protein-5; osteoblast; protein kinase C; messenger RNA; protein kinase A;
D O I
10.1152/ajpendo.00417.2001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 muM bovine PTH-(3-34) stimulated a 10-fold induction of IGFBP-5 mRNA. PTH-(1-34) and PTH-(3-34) (100 nM) both stimulated PKC-delta translocation from the membrane to the nuclear fraction. Rottlerin, a PKC-delta-specific inhibitor, and a dominant negative mutant of PKC-delta were both able to significantly inhibit PTH-(1-34) and PTH-(3-34) induction of IGFBP-5 mRNA, suggesting a stimulatory role for PKC-delta in the effects of PTH. Phorbol 12-myristate 13-acetate (PMA) stimulated PKC-alpha translocation from the cytosol to the membrane and inhibited similar to50% of the PTH-(1-34), forskolin, and 8-bromoadenosine 3', 5'-cyclic monophosphate-stimulated IGFBP-5 mRNA levels, suggesting that PKC-alpha negatively 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 PKC-delta is the primary mediator of the effects of PTH via the PKC pathway.
引用
收藏
页码:E534 / E541
页数:8
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