Rapid increase of the human IFN-gamma receptor phosphorylation in response to human IFN-gamma and phorbol myristate acetate. Involvement of different serine/threonine kinases.

Détails

ID Serval
serval:BIB_C65C402F4642
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Rapid increase of the human IFN-gamma receptor phosphorylation in response to human IFN-gamma and phorbol myristate acetate. Involvement of different serine/threonine kinases.
Périodique
Journal of Immunology
Auteur⸱e⸱s
Mao C., Merlin G., Ballotti R., Metzler M., Aguet M.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
1990
Volume
145
Numéro
12
Pages
4257-4264
Langue
anglais
Résumé
Various cell surface receptors are phosphorylated upon binding of their ligand, and this phosphorylation seems to be involved in the signal transduction or in the feedback regulation of this signal. The possibility of a phosphorylation of the human IFN-gamma receptor (hu-IFN-gamma-R) has been investigated with 32P-labeled whole Raji cells and receptor purification either by immunoprecipitation with an anti-hu-IFN-gamma-R polyclonal antiserum or by affinity chromatography. The hu-IFN-gamma-R was found to be phosphorylated at a basal level. Upon incubation of the cells with recombinant hu-IFN-gamma, a dose-dependent two-fold increase of this phosphorylation was observed. Phosphoamino acid analysis by TLC showed that the same amino acids, serine and threonine, are phosphorylated at a basal level and after incubation with hu-IFN-gamma. Protein kinase C and Ca2+/calmodulin-dependent kinase pathways have been reported in some cases to be involved in the signal transduction pathway of hu-IFN-gamma. Both pathways involved the activation of a serine/threonine kinase and therefore we have investigated the possibility of hu-IFN-gamma-R phosphorylation by these kinases. PMA, an activator of protein kinase C, induced a rapid increase of the receptor phosphorylation in Raji cells, whereas the Ca2+ ionophore A23187 did not. PMA-induced hu-IFN-gamma-R phosphorylation was not associated with any effect on expression or inactivation of the receptor. PMA alone did not mimic the hu-IFN-gamma effect in Raji cells as measured by induction of IP-10 gene expression, a high specific marker of hu-IFN-gamma response. But the protein kinase C inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and staurosporine, reduced this IFN-gamma-induced expression. However, H7 and staurosporine treatment as well as protein kinase C depletion suppressed PMA-induced receptor phosphorylation, whereas constitutive and hu-IFN-gamma-induced phosphorylation remained unchanged. Our results suggest that the serine/threonine kinase involved in the hu-IFN-gamma-R phosphorylation induced by IFN-gamma is different from protein kinase C.
Mots-clé
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Alkaloids/pharmacology, Blotting, Northern, Humans, Interferon-gamma/pharmacology, Isoquinolines/pharmacology, Molecular Weight, Phosphoproteins/metabolism, Phosphorylation, Phosphoserine/metabolism, Phosphothreonine/metabolism, Piperazines/pharmacology, Protein Kinases/metabolism, RNA, Messenger/metabolism, Receptors, Immunologic/metabolism, Receptors, Interferon, Staurosporine, Sulfonamides/pharmacology, Tetradecanoylphorbol Acetate/pharmacology, Time Factors
Pubmed
Web of science
Création de la notice
28/01/2008 11:36
Dernière modification de la notice
20/08/2019 15:41
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