Nucleotides stimulate phospholipasc D activity in hepatic stellate cells: evidence for the involvement of a single nucleotide receptor, protein kinase C and a pertussis toxin insensitive guanine-nucleotide binding protein

2000 ◽  
Vol 28 (5) ◽  
pp. A265-A265
Author(s):  
J. Benitez ◽  
M-J Lorite ◽  
AD Burt ◽  
CP Day ◽  
MG Thompson
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Receptor Protein ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Binding Protein ◽  
Single Nucleotide ◽  
Kinase C ◽  
Guanine Nucleotide Binding

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.

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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