TY - JOUR
T1 - Specific regulation of the 100 kDa 2-5 A synthetase by protein kinase C.
AU - Raber, J.
AU - Eldar, H.
AU - Lehrer, R.
AU - Chebath, J.
AU - Livneh, E.
N1 - Copyright:
This record is sourced from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
PY - 1991
Y1 - 1991
N2 - The 2-5 A synthetase is a system of several isozymes, whose expression is induced by interferons (IFNs) at the transcriptional level. These enzymes mediate part of the antiviral effects of IFNs and are thought to have an important role in cell growth or differentiation. The different isozymes -100, 69, 46 and 40 kDa expressed in human cells, or the 105, 71 and 43 kDa expressed in mouse cells--are induced by IFNs with cell type specificity, and exhibit individual differences in their biochemical and enzymatic properties. Here we studied the effects of the tumor promoter phorbol ester (TPA), or the calcium ionophore A23187, on the pattern of expression of 2-5 A synthetase isoforms, and found a role of protein kinase C (PKC) in the adjustments of this pattern. We show that in HeLa cells the 100 kDa 2-5 A synthetase can be specifically induced by short term treatments with TPA, or with the calcium ionophore A23187. Induction of the 100 kDa form is mainly post-transcriptional. By contrast long term treatments by TPA resulting in the down regulation of PKC, or employing H7, a specific PKC inhibitor, reduced drastically the induction by IFNs of the 100 kDa enzyme in HeLa or fibroblast cells, without reducing the expression of the other forms. Moreover, using a mouse Swiss 3T3 cell line in which the cDNA coding for PKC-alpha was introduced, leading to its overexpression, we could show that the mouse 105 kDa synthetase was constitutively expressed. Thus, a direct correlation was found between the expression of PKC-alpha and the specific induction of the 105 kDa form. Neutralization of autocrine IFNs by antibodies reduces the expression of the 105 kDa species. However the autocrine IFN in the medium of the cells overexpressing PKC is not able to induce 2-5 A synthetase in control transfected Swiss 3T3 cells. Thus, IFN is probably essential for the expression of the 105 kDa synthetase but may be not produced in sufficient amounts to induce the 105 kDa protein.
AB - The 2-5 A synthetase is a system of several isozymes, whose expression is induced by interferons (IFNs) at the transcriptional level. These enzymes mediate part of the antiviral effects of IFNs and are thought to have an important role in cell growth or differentiation. The different isozymes -100, 69, 46 and 40 kDa expressed in human cells, or the 105, 71 and 43 kDa expressed in mouse cells--are induced by IFNs with cell type specificity, and exhibit individual differences in their biochemical and enzymatic properties. Here we studied the effects of the tumor promoter phorbol ester (TPA), or the calcium ionophore A23187, on the pattern of expression of 2-5 A synthetase isoforms, and found a role of protein kinase C (PKC) in the adjustments of this pattern. We show that in HeLa cells the 100 kDa 2-5 A synthetase can be specifically induced by short term treatments with TPA, or with the calcium ionophore A23187. Induction of the 100 kDa form is mainly post-transcriptional. By contrast long term treatments by TPA resulting in the down regulation of PKC, or employing H7, a specific PKC inhibitor, reduced drastically the induction by IFNs of the 100 kDa enzyme in HeLa or fibroblast cells, without reducing the expression of the other forms. Moreover, using a mouse Swiss 3T3 cell line in which the cDNA coding for PKC-alpha was introduced, leading to its overexpression, we could show that the mouse 105 kDa synthetase was constitutively expressed. Thus, a direct correlation was found between the expression of PKC-alpha and the specific induction of the 105 kDa form. Neutralization of autocrine IFNs by antibodies reduces the expression of the 105 kDa species. However the autocrine IFN in the medium of the cells overexpressing PKC is not able to induce 2-5 A synthetase in control transfected Swiss 3T3 cells. Thus, IFN is probably essential for the expression of the 105 kDa synthetase but may be not produced in sufficient amounts to induce the 105 kDa protein.
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M3 - Article
C2 - 1756233
AN - SCOPUS:0026200323
SN - 1148-5493
VL - 2
SP - 281
EP - 290
JO - European cytokine network
JF - European cytokine network
IS - 4
ER -