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Modulation of human platelet-activating factor receptor gene expression by protein kinase C activation.
J Immunol. 1996 Nov 15; 157(10):4681-7.JI

Abstract

The effect of PMA on early and late regulation of platelet-activating factor receptor (PAF-R) expression was examined in human monocytes. Treatment with 16 nM PMA for 5 min initiated a rapid reduction (50-75%) in [3H]WEB 2086 binding, which was maximal between 5 and 15 min. Scatchard analysis revealed that PMA treatment reduced the number of binding sites to 50% of control cells without an appreciable change in their affinity. In parallel cultures, flow cytometry analysis using anti-PAF-R Abs failed to reveal any significant decrease in the level of PAF-R expression until after 4 h of treatment with PMA. By 24 h, PAF-R expression had declined by 80 to 90%. This PMA-induced down-regulation of surface PAF-R expression was preceded by a rapid down-regulation of PAF-R mRNA expression. PMA-mediated down-regulation could be blocked by the protein kinase C (PKC) inhibitors H-7 and calphostin C. Activation of PKC by the diacylglycerol analogue 1-oleoyl-2-acetylglycerol also resulted in down-regulation of PAF-R mRNA accumulation, whereas the inactive phorbol diester 4alpha-PMA was ineffective. The rapid disappearance of the PAF-R transcripts was associated with decreased stability of receptor mRNA and not with a change in the nuclear transcription rate of the PAF-R gene. These findings indicate that PAF-R gene expression in human leukocytes can be regulated through a PKC-dependent pathway and involves post-transcriptional destabilization of receptor mRNA.

Authors+Show Affiliations

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8906849

Citation

Thivierge, M, et al. "Modulation of Human Platelet-activating Factor Receptor Gene Expression By Protein Kinase C Activation." Journal of Immunology (Baltimore, Md. : 1950), vol. 157, no. 10, 1996, pp. 4681-7.
Thivierge M, Parent JL, Stankova J, et al. Modulation of human platelet-activating factor receptor gene expression by protein kinase C activation. J Immunol. 1996;157(10):4681-7.
Thivierge, M., Parent, J. L., Stankova, J., & Rola-Pleszczynski, M. (1996). Modulation of human platelet-activating factor receptor gene expression by protein kinase C activation. Journal of Immunology (Baltimore, Md. : 1950), 157(10), 4681-7.
Thivierge M, et al. Modulation of Human Platelet-activating Factor Receptor Gene Expression By Protein Kinase C Activation. J Immunol. 1996 Nov 15;157(10):4681-7. PubMed PMID: 8906849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of human platelet-activating factor receptor gene expression by protein kinase C activation. AU - Thivierge,M, AU - Parent,J L, AU - Stankova,J, AU - Rola-Pleszczynski,M, PY - 1996/11/15/pubmed PY - 1996/11/15/medline PY - 1996/11/15/entrez SP - 4681 EP - 7 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 157 IS - 10 N2 - The effect of PMA on early and late regulation of platelet-activating factor receptor (PAF-R) expression was examined in human monocytes. Treatment with 16 nM PMA for 5 min initiated a rapid reduction (50-75%) in [3H]WEB 2086 binding, which was maximal between 5 and 15 min. Scatchard analysis revealed that PMA treatment reduced the number of binding sites to 50% of control cells without an appreciable change in their affinity. In parallel cultures, flow cytometry analysis using anti-PAF-R Abs failed to reveal any significant decrease in the level of PAF-R expression until after 4 h of treatment with PMA. By 24 h, PAF-R expression had declined by 80 to 90%. This PMA-induced down-regulation of surface PAF-R expression was preceded by a rapid down-regulation of PAF-R mRNA expression. PMA-mediated down-regulation could be blocked by the protein kinase C (PKC) inhibitors H-7 and calphostin C. Activation of PKC by the diacylglycerol analogue 1-oleoyl-2-acetylglycerol also resulted in down-regulation of PAF-R mRNA accumulation, whereas the inactive phorbol diester 4alpha-PMA was ineffective. The rapid disappearance of the PAF-R transcripts was associated with decreased stability of receptor mRNA and not with a change in the nuclear transcription rate of the PAF-R gene. These findings indicate that PAF-R gene expression in human leukocytes can be regulated through a PKC-dependent pathway and involves post-transcriptional destabilization of receptor mRNA. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8906849/Modulation_of_human_platelet_activating_factor_receptor_gene_expression_by_protein_kinase_C_activation_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=8906849 DB - PRIME DP - Unbound Medicine ER -