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Activation of protein kinase C via the T-cell receptor complex potentiates cyclic AMP responses in T-cells

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Summary

We have recently shown that activation of protein kinase C by tumour promoting phorbolesters, such as 4β-β-phorbol-12,13-dibutyrate, stimulates adenosine-induced accumulation of cAMP in 7urkat cells, a human T-leukaemia line. Activating the CD3 complex associated with the T-cell receptor by means of the monoclonal antibody OKT3 caused a concentration-dependent accumulation of inositol phosphates and an increase in the phosphorylation of an endogenous protein kinase C substrate. OKT3 also mimicked the previously reported effects of protein kinase C since it potentiated the cAMP stimulation by either an adenosine analogue, NECA, or cholera toxin. Thus, our results indicate that stimulation of a receptor activating phospholipase C and protein kinase C can secondarily enhance the action of agonists that act on adenylate cyclase-coupled receptors.

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Abbreviations

cAMP:

cyclic adenosine-monophosphate

NECA:

5′-N-ethylcarboxyamido adenosine

References

  • Averill LE, Stein RL, Kammer GM (1988) Control of human Tlymphocyte interleukin-2 production by a cAMP-dependent pathway. Cell Immunol 115:88–99

    Google Scholar 

  • Beckner SK, Farrar WL (1986) Interleukin-2 modulation of adenylate cyclase: potential role of protein kinase C. J Biol Chem 261:3043–3047

    Google Scholar 

  • Berridge MJ, Dawson RMC, Downes CP, Heslop JP, Irvine RF (1983) Changes in the level of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J 212:473–482

    Google Scholar 

  • Brown BL, Albano JDM, Ekins RP, Sgherzi AM, Tampion W (1971) A simple and sensitive saturation assay method for the measurement of adenosine 3,5-cyclic monophosphate. Biochem J 121:561–562

    Google Scholar 

  • Fredholm BB, Sollevi A (1986) Cardiovascular effects of adenosine. Clin Physiol 6:1–21

    Google Scholar 

  • Friedrich B, Noreus K, Cantrell DA, Gullberg M (1988) Activation dependent phosphorylation of endogenous protein kinase C substrate in quiescent human T-lymphocytes. Immunobiology 176:465–478

    Google Scholar 

  • Goldsmith MA, Weiss A (1988) New clues about the T-cell antigen receptor complex function. Immunol Today 9:220–222

    Google Scholar 

  • Hollingsworth EB, Sears EB, Daly JW (1985) An activator of protein kinase C (phorbol-l2-myristate-13-acetate) augments 2-chloroadenosine-elicited accumulation of cyclic AMP in guinea pig cerebral cortical particulate preparations. FEBS Lett 184:339–342

    Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    PubMed  Google Scholar 

  • Lerner A, Jacobson B, Miller RA (1988) Cyclic AMP concentrations modulate both calcium flux and hydrolysis of phosphatidylinositol phosphates in mouse T lymphocytes. J Immunol 140:936–940

    Google Scholar 

  • Manger B, Weiss A, Imboden J, Laing T, Stobo JD (1987) The role of protein kinase C in transmembrane signalling by the T-cell antigen receptor complex. J Immunol 139:2755–2760

    Google Scholar 

  • Ng J, Fredholm BB, Jondal M, Anderson T (1987) Characterization of PHA and anti-T3 induced transduction mechanisms in a human T-cell leukemia. Int J Immunopharmacol 9:17–22

    Google Scholar 

  • Nishizuka Y (1986) Studies and perspectives of protein kinase C. Science 233:305–312

    CAS  PubMed  Google Scholar 

  • Nordstedt C, Fredholm BB (1987) Phorbol-12,13-dibutyrate enhances the cyclic AMP accumulation in rat hippocampal slices induced by adenosine analogues. Naunyn-Schmiedeberg's Arch Pharmacol 335:136–142

    Google Scholar 

  • Nordstedt C, Jondal M, Fredholm BB (1987) Activation of protein kinase C inhibits prostaglandin- and potentiates adenosine-receptor stimulated accumulation of cyclic AMP in a human T-cell leukemia line. FEBS Lett 220:57–60

    Google Scholar 

  • Nordstedt C, Kvanta A, Van der Ploeg I, Fredholm BB (1989) Dual effects of protein kinase C receptor stimulated cAMP accumulation in a human T-cell leukemia line. Eur J Pharmacol Mol Pharmacol Sect 1:51–60

    Google Scholar 

  • Patel MD, Samelson LE, Klausner RD (1987) Multiple kinase in signal transduction: phosphorylation of the T-cell antigen receptor. J Biol Chem 262:5831–5838

    Google Scholar 

  • Weiss A, Imboden J, Shoback D, Stobo J (1984) Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium. Proc Natl Acad Sci [USA] 81:4169–4173

    Google Scholar 

  • Wiener E, Scarpa A (1989) Activation of protein kinase C modulates the adenylate cyclase effector system in B-lymphocytes. J Biol Chem 264:4324–4328

    Google Scholar 

  • Yoshimasa T, Sibley DR, Bouvier M, Lefkowitz RJ, Caron MG (1987) Cross-talk between cellular signalling pathways suggested by phorbol ester induced adenylate cyclase phosphorylation. Nature 327:67–70

    Google Scholar 

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The present study was supported by grants from The Swedish Cancer Association, The Swedish Medical Research Council (project no. 2553), by Gustaf V 80 Years Fund, by Nanna Swartz foundation and by Karolinska Institutet

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Kvanta, A., Nordstedt, C., Jondal, M. et al. Activation of protein kinase C via the T-cell receptor complex potentiates cyclic AMP responses in T-cells. Naunyn-Schmiedeberg's Arch Pharmacol 340, 715–717 (1989). https://doi.org/10.1007/BF00169679

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  • DOI: https://doi.org/10.1007/BF00169679

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