1,25-dihydroxyvitamin D3 stimulated protein kinase C phosphorylation of type VI adenylyl cyclase inhibits parathyroid hormone signal transduction in rat osteoblastic UMR 106-01 cells

2005 ◽  
Vol 94 (5) ◽  
pp. 1017-1027 ◽  
Author(s):  
Ricky Cheung ◽  
Mary S. Erclik ◽  
Jane Mitchell
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Kinase C ◽  
Umr 106

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.

Involvement of protein kinase C in the stimulation of sodium-dependent phosphate transport by parathyroid hormone in osteoblast-like cells

1994 ◽  
Vol 131 (6) ◽  
pp. 646-651 ◽  
Author(s):  
Makoto Arao ◽  
Toru Yamaguchi ◽  
Toshitsugu Sugimoto ◽  
Masaaki Fukase ◽  
Kazuo Chihara
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Calcium Ionophore ◽  
Cytosolic Calcium ◽  
Phosphate Transport ◽  
Osteosarcoma Cell ◽  
Kinase C ◽  
Umr 106

Arao M, Yamaguchi T, Sugimoto T, Fukase M, Chihara K. Involvement of protein kinase C in sodiumdependent phosphate transport by parathyroid hormone in osteoblast-like cells. Eur J Endocrinol 1994;131:646–51. ISSN 0804–4643 The rat osteosarcoma cell line UMR-106 has an osteoblast-like phenotype and possesses parathyroid hormone (PTH)-responsive dual signal transduction systems [adenosine 3′,5′-cyclic monophosphatedependent protein kinase (PKA) and calcium-protein kinase C (Ca-PKC)]. These cells transport inorganic phosphate (Pi) by a Na+-dependent carrier under stimulation by PTH. The present study aimed to clarify PTH-responsive signal transduction mechanisms in the regulation of Na+-dependent Pi transport by PTH in UMR-106 cells. Exposure of these cells to 10−7 mol/l PTH induced a significant increase in Pi uptake within 30 min of incubation and it became maximal after 2 h. Parathyroid hormone (10−9 –10−7 mol/l) stimulated Pi uptake dose dependently. Activation of PKC by 12-O-tetradecanoyl phorbol- 13-acetate (TPA) also increased Pi uptake in time- and dose-dependent manners similar to PTH In contrast, neither PKA activation by 10 mol/l forskolin or by 10−4 mol/l dibutyryladenosine 3′,5′-cyclic monophosphate nor calcium ionophore treatment with 10−7 mol/l A23187 or with 10−7 mol/l ionomycin during 3-h incubations affect Pi uptake, except its increase by 10−4 mol/l forskolin at a 3-h incubation. These agents had no influence on Pi uptake even in combined treatments with TPA. The PTH-induced increase in Pi uptake was abolished almost completely by pretreating cells with PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 μmol/l) or staurosporin (10 and 50 nmol/l), and by down-regulating PKC with a prolonged TPA treatment. These results indicate that the messenger system mediated by PKC, rather than by PKA or by cytosolic calcium, plays a crucial role in the regulation of Na+-dependent Pi transport by PTH within a few hours of exposure of the hormone in the osteoblast-like cells. Toru Yamaguchi, Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650, Japan

Effects of parathyroid hormone and agonists of the adenylyl cyclase and protein kinase C pathways on bone cell proliferation

Bone ◽  
1996 ◽  
Vol 18 (1) ◽  
pp. 59-65 ◽  
Author(s):  
M. Sabatini ◽  
C. Lesur ◽  
M. Pacherie ◽  
P. Pastoureau ◽  
N. Kucharczyk ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase C ◽  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Bone Cell ◽  
Kinase C ◽  
Bone Cell Proliferation
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