Phospholipase C gamma 1 overexpression and activation induced by interferon beta in human T lymphocytes: an ISGF3-independent response.
Interferons exert their antiviral, antiproliferative and immunoregulatory activities by stimulating the expression of several genes. Such genes disclose a common element within their promoters, defined Interferon Stimulated Response Element (ISRE), which binds a nuclear factor(s) translocated from the cytoplasm to the nucleus (ISGF3) after the binding of interferon (IFN) to the specific receptor. Here we report the induction of the synthesis and of the hydrolytic activity of phospholipase C gamma 1 (PLC gamma 1) in human T lymphocytes by IFN-beta. The increased level of PLC gamma 1 becomes evident after 90 min of IFN-beta treatment and is still detectable after 24 h. Neither the PLC gamma 1 overexpression induced by IFN nor the increased hydrolytic activity of the enzyme appear to be affected by pretreatment of the cells with the protein tyrosine kinase inhibitor genistein, which is known to prevent the association of ISGF3 components. These results suggest that in human T lymphocytes IFN-beta can activate other transcription factor(s) distinct from ISGF3 to regulate PLC gamma 1 expression. In addition, the ability of this enzyme to hydrolyse PIP2, also in the presence of genistein, implies the possibility that this enzyme can exert its hydrolytic activity independently of protein tyrosine kinase activation.
Miscia
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Istituto di Morfologia Umana, Università G. D'Annunzio, Chieti, Italy. s.miscia@morpho.unich.it
Di Baldassarre
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Rana
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Cataldi
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D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016899:Interferon-beta / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D018613:Microscopy, Confocal; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010835:Phytohemagglutinins; D014157:Transcription Factors; C028784:phytohemagglutinin-P; D016899:Interferon-beta; D019833:Genistein; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D051966:Phospholipase C gamma