Abstract
Bacterial lipopolysaccharide (LPS) induces a strong B-cell proliferative response with subsequent differentiation, through a complex signal transduction pathway. This process is known to be mediated through protein kinase C (PKC) translocation without Ca2+ mobilization. Here, we show that B-cell proliferative responses induced by five different LPS preparations, as well as by F(ab')2 anti-IgM antibodies, are inhibited by the tyrosine kinase inhibitors, genistein and herbimycin A. In contrast, B-cell proliferation induced by the combination of phorbol 12-myristate 13-acetate (PMA) plus ionomycin was not influenced by treatment with either herbimycin A or genistein. These data indicate that tyrosine phosphorylation is required to initiate B-cell proliferation by LPS.
Full text
PDF


Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aderem A. A., Albert K. A., Keum M. M., Wang J. K., Greengard P., Cohn Z. A. Stimulus-dependent myristoylation of a major substrate for protein kinase C. Nature. 1988 Mar 24;332(6162):362–364. doi: 10.1038/332362a0. [DOI] [PubMed] [Google Scholar]
- Akiyama T., Ishida J., Nakagawa S., Ogawara H., Watanabe S., Itoh N., Shibuya M., Fukami Y. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987 Apr 25;262(12):5592–5595. [PubMed] [Google Scholar]
- Bijsterbosch M. K., Rigley K. P., Klaus G. G. Cross-linking of surface immunoglobulin on B lymphocytes induces both intracellular Ca2+ release and Ca2+ influx: analysis with indo-1. Biochem Biophys Res Commun. 1986 May 29;137(1):500–506. doi: 10.1016/0006-291x(86)91238-6. [DOI] [PubMed] [Google Scholar]
- Cambier J. C., Ransom J. T. Molecular mechanisms of transmembrane signaling in B lymphocytes. Annu Rev Immunol. 1987;5:175–199. doi: 10.1146/annurev.iy.05.040187.001135. [DOI] [PubMed] [Google Scholar]
- Campbell M. A., Sefton B. M. Protein tyrosine phosphorylation is induced in murine B lymphocytes in response to stimulation with anti-immunoglobulin. EMBO J. 1990 Jul;9(7):2125–2131. doi: 10.1002/j.1460-2075.1990.tb07381.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carter R. H., Park D. J., Rhee S. G., Fearon D. T. Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2745–2749. doi: 10.1073/pnas.88.7.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Z. Z., Coggeshall K. M., Cambier J. C. Translocation of protein kinase C during membrane immunoglobulin-mediated transmembrane signaling in B lymphocytes. J Immunol. 1986 Mar 15;136(6):2300–2304. [PubMed] [Google Scholar]
- Dziarski R. Correlation between ribosylation of pertussis toxin substrates and inhibition of peptidoglycan-, muramyl dipeptide- and lipopolysaccharide-induced mitogenic stimulation in B lymphocytes. Eur J Immunol. 1989 Jan;19(1):125–130. doi: 10.1002/eji.1830190120. [DOI] [PubMed] [Google Scholar]
- Jakway J. P., DeFranco A. L. Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide. Science. 1986 Nov 7;234(4777):743–746. doi: 10.1126/science.3095921. [DOI] [PubMed] [Google Scholar]
- June C. H., Fletcher M. C., Ledbetter J. A., Schieven G. L., Siegel J. N., Phillips A. F., Samelson L. E. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722–7726. doi: 10.1073/pnas.87.19.7722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klaus G. G., O'Garra A., Bijsterbosch M. K., Holman M. Activation and proliferation signals in mouse B cells. VIII. Induction of DNA synthesis in B cells by a combination of calcium ionophores and phorbol myristate acetate. Eur J Immunol. 1986 Jan;16(1):92–97. doi: 10.1002/eji.1830160118. [DOI] [PubMed] [Google Scholar]
- Li Y. S., Dearden-Badet M. T., Revillard J. P. Selective induction of high levels of IgA synthesis in Peyer's patch B cells by protein kinase C-activating phorbol esters. J Immunol. 1991 Sep 15;147(6):1752–1758. [PubMed] [Google Scholar]
- Obinata A., Akimoto Y., Hirano H., Endo H. Stimulation by Bt2cAMP of epidermal mucous metaplasia in retinol-pretreated chick embryonic cultured skin, and its inhibition by herbimycin A, an inhibitor for protein-tyrosine kinase. Exp Cell Res. 1991 Mar;193(1):36–44. doi: 10.1016/0014-4827(91)90535-3. [DOI] [PubMed] [Google Scholar]
- Rosoff P. M., Cantley L. C. Lipopolysaccharide and phorbol esters induce differentiation but have opposite effects on phosphatidylinositol turnover and Ca2+ mobilization in 70Z/3 pre-B lymphocytes. J Biol Chem. 1985 Aug 5;260(16):9209–9215. [PubMed] [Google Scholar]
- Rush J. S., Waechter C. J. Inhibitors of protein kinase C block activation of B lymphocytes by bacterial lipopolysaccharide. Biochem Biophys Res Commun. 1987 Jun 30;145(3):1315–1320. doi: 10.1016/0006-291x(87)91581-6. [DOI] [PubMed] [Google Scholar]
- Uehara Y., Murakami Y., Sugimoto Y., Mizuno S. Mechanism of reversion of Rous sarcoma virus transformation by herbimycin A: reduction of total phosphotyrosine levels due to reduced kinase activity and increased turnover of p60v-src1. Cancer Res. 1989 Feb 15;49(4):780–785. [PubMed] [Google Scholar]
