Protein kinase C potentiates PTH-mediated stimulation of cyclic AMP production via the αGi2 guanine nucleotide-binding protein in UMR-106 osteosarcoma cells

1992 ◽  
Vol 17 ◽  
pp. 197
Author(s):  
H.M. Koch ◽  
H. Muir ◽  
D. Gelderblom ◽  
F.S. Hough
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Guanine Nucleotide ◽  
Osteosarcoma Cells ◽  
Guanine Nucleotide Binding Protein ◽  
Kinase C ◽  
Guanine Nucleotide Binding ◽  
Umr 106 ◽  
Stimulation Of

scholarly journals Okadaic acid identifies a phosphorylation/dephosphorylation cycle controlling the inhibitory guanine-nucleotide-binding regulatory protein Gi2

1991 ◽  
Vol 274 (2) ◽  
pp. 317-321 ◽  
Author(s):  
M Bushfield ◽  
B E Lavan ◽  
M D Houslay
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Okadaic Acid ◽  
Regulatory Protein ◽  
Nucleotide Binding ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Binding Protein ◽  
Kinase C ◽  
Guanine Nucleotide Binding

Recently, the alpha-subunit of the inhibitory guanine-nucleotide-binding protein Gi2 (alpha-Gi2) has been shown to be a substrate for phosphorylation both by protein kinase C and also by other unidentified kinase(s) which are activated as a result of elevated cyclic AMP levels in intact rat hepatocytes [Bushfield, Murphy, Lavan, Parker, Hruby, Milligan & Houslay (1990) Biochem. J. 268, 449-457]. Here we show that the incorporation of [32P]Pi into alpha-Gi2 was enhanced 3-fold by incubation of intact hepatocytes with the tumour promoter and protein phosphatase (1 and 2A) inhibitor, okadaic acid. This action was both time- and concentration-dependent and was accompanied by a loss of guanine-nucleotide-induced inhibition of adenylate cyclase. The increased labelling of alpha-Gi2 induced by okadaic acid was partially additive with that elicited by 8-bromo cyclic AMP, but not with that elicited by the protein kinase C activator phorbol 12-myristate 13-acetate. We suggest that, in the absence of hormones, the activity of alpha-Gi2 is under the control of a dynamic phosphorylation/dephosphorylation system involving protein kinase C and protein phosphatases 1 and/or 2A. This highlights the regulation of kinases and phosphatases as both providing potentially important mechanisms for causing ‘cross-talk’ between different signalling systems, in this instance controlling cellular responsiveness through regulation of alpha-Gi2 phosphorylation.

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.

A Possible Role for Protein Kinase C in the Regulatory Differences between Intra-Abdominal and Subcutaneous Human Adipose Tissue

1993 ◽  
Vol 85 (3) ◽  
pp. 265-268 ◽  
Author(s):  
Hanna-Leena Vikman ◽  
Johanna M. Kaartinen ◽  
Raimo K. Tuominen ◽  
Jorma J. Ohisalo
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein S ◽  
Nucleotide Binding ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Binding Protein ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Guanine Nucleotide Binding

1. The adenosine A1-receptor agonist N6-(phenylisopropyl)adenosine inhibited lioplysis in a dose-dependent manner in human adipocytes. The effect is mediated by the inhibitory guanine-nucleotide-binding protein(s) that can be phosphory-lated and thereby inactivated by protein kinase C. 2. Stimulation of protein kinase C by 12-O-tetradecanoyl-phorbol-13-acetate attenuated the inhibitory effect of the adenosine agonist. 3. Omental fat cells are less sensitive to adenosine than subcutaneous cells, although the stimulatory arm of cyclase regulation appears normal. Protein kinase C activity was measured in the soluble and particulate fractions of human omental and subcutaneous adipose tissue. Omental adipose tissue had a twofold higher membrane-bound and a threefold higher soluble protein kinase C activity. 4. It is therefore possible that the differences in regulation between the two sites are caused by different C kinase activities, causing variable phosphorylation of the inhibitory guanine-nucleotide-binding protein(s).

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