Parathyroid hormone stimulates translocation of protein kinase C isozymes in UMR-106 osteoblastic osteosarcoma cells

Bone ◽  
2001 ◽  
Vol 29 (3) ◽  
pp. 223-230 ◽  
Author(s):  
D.A Dossing ◽  
J.M Radeff ◽  
J Sanders ◽  
S.-K Lee ◽  
M.-R Hsieh ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Osteosarcoma Cells ◽  
Kinase C ◽  
Umr 106 ◽  
Osteoblastic Osteosarcoma

Protein kinase C activating phorbolesters enhance the cyclic AMP response to parathyroid hormone, forskolin and choleratoxin in mouse calvarial bones and rat osteosarcoma cells

1991 ◽  
Vol 11 (4) ◽  
pp. 203-211 ◽  
Author(s):  
Maria Ransjö
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Phorbol Esters ◽  
Osteosarcoma Cells ◽  
Kinase C ◽  
Cyclic Amp Accumulation ◽  
Umr 106

The protein kinase C-(PKC) activating phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nmol/l) and phorbol 12, 13-dibutyrate (PDBU; 100 nmol/l) enhanced basal cyclin AMP accumulation in cultured neonatal mouse calvaria. The cyclic AMP response to parathyroid hormone (PTH; 10 nmol/l) and the adenylate cyclase activators forskolin (1–3 μmol/l) and choleratoxin (0.1 μmg/ml) was potentiated in a more than additive manner by TPA and PDBU. In contrast, phorbol 13-monoacetate (phorb-13; 100 nmol/l), a related compound but inactive on PKC, had no effect on basal or stimulated cyclic AMP accumulation. In the presence of indomethacin (1μmol/l), TPA and PDBU had no effect on cyclic AMP accumulation in calvarial bones per se, but were still able to cause a significant enhancement of the response to PTH, forskolin and choleratoxin. PTH-, forskolin- and choleratoxin-stimulated cyclic AMP accumulation in rat osteosarcoma cells UMR 106-01 was synergistically potentiated by TPA and PDBU, but not by phorb.-13. These data indicate that PKC enhances cyclic AMP formation and that the level of interaction may be at, or distal to, adenylate cyclase.

Bidirectional modulation of parathyroid hormone-responsive adenylyl cyclase by protein kinase C

1994 ◽  
Vol 266 (6) ◽  
pp. E897-E904 ◽  
Author(s):  
A. M. Kitten ◽  
T. K. Hymer ◽  
M. S. Katz
Keyword(s):  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Catalytic Subunit ◽  
Mrna Levels ◽  
Binding Studies ◽  
Kinase C ◽  
Bidirectional Modulation ◽  
Umr 106

The temporal pattern with which phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), modulates parathyroid hormone (PTH)-responsive adenylyl cyclase (AC) was evaluated in a clonal osteoblast-like cell line (UMR-106). Brief (< or = 1 h) exposure of UMR-106 cells to PMA enhanced PTH stimulation of AC, whereas more prolonged PMA treatment decreased the PTH response, with maximum inhibition occurring at < or = 6 h. PMA treatment also resulted in initial activation followed by downregulation of PKC. Exposure of cells to 1,2-dioctanoyl-sn-glycerol, which activated but did not downregulate PKC, resulted in bidirectional modulation of PTH-responsive AC identical to that produced by PMA. Prolonged PMA exposure decreased PTH receptor number, as determined by radioligand binding studies, and reduced PTH receptor mRNA levels, assessed by Northern blot analysis. Forskolin activation of the catalytic subunit of AC was also decreased after prolonged PMA treatment. The results suggest that activation of PKC sequentially stimulates and then inhibits PTH responsiveness. Inhibition of the PTH response occurs by PKC actions exerted on the PTH receptor and the AC catalytic subunit.

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