Opposing Effects of Protein Kinase C on IgE-Dependent Exocytosis and InsP3 Formation

  • G. Gat-Yablonski
  • R. Sagi-Eisenberg
Conference paper
Part of the NATO ASI Series book series (volume 56)

Abstract

Aggregation of the receptors for Immunoglobulin E (IgE) by a multivalent antigen (Ag) leads to activation of phospholipase C (PLC) and secretion of serotonin from Rat Basophilic Leukemia (RBL) cells. The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA), exerts dual actions on the IgE-dependent responses in RBL cells: TPA potentiates IgE- induced secretion but it inhibits IgE-induced InsP3 formation and the subsequent rise in internal Ca2+ concentrations. In addition, TPA synergizes with Ca2+ ionophores to trigger exocytosis. We have undertaken this study to examine whether the dual actions of TPA are both mediated by protein kinase C (PKC). It is relevant to evaluate the participation of PKC in TPA actions since some reports suggest that not all TPA actions are consequences of TPA binding and activation of PKC (Zick et al. (1985); Maraganore, J.M. (1987)). In addition, PKC consists of a family of enzymes that while closely related in structure (reviewed in Nishizuka, Y. (1988)), they differ in their cellular and intracellular disributions as well as in their responses to cofactors such as Ca2+, diacylglycerol (DAG), phosphatidylserine (PS) and fatty acids (Nishizuka, Y. (1988)). We have therefore analyzed the possibility that different isozymes of PKC may be involved in mediating the opposing effects of TPA on the IgE-mediated responses in RBL cells.

Keywords

Tyrosine Leukemia Serotonin Dimethyl Phorbol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ase K, Berry N, Kikkawa U, Kishimoto A, Nishizuka Y (1988) Differential down-regulation of protein kinase C subspecies in KM3 cells. FEBS Lett 236: 396–400PubMedCrossRefGoogle Scholar
  2. Gat-Yablonski G, Sagi-Eisenberg R (1990) Differential down-regulation of protein kinase C selectively affects IgE-dependent exocytosis and inositol trisphosphate formation. Biochem J 270: 679–684.PubMedGoogle Scholar
  3. Hannun YA, Locmis CR, Merrill AJ Jr, Bell KM (1986) Sphingosine inhibiticn of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets. J Biol Chem 261: 12604–12609PubMedGoogle Scholar
  4. Huang FL, Yoshida Y, Cunha-Melo JR, Beaven MA, Huang KP (1989) Differential down-regulation of protein kinase C isozymes. J Biol Chem 264: 4243Google Scholar
  5. Kase H, Iwahasi K, Matsuda Y (1986) K-252a, a potent inhibitor of protein kinase C from microbial origin. J Antibiot 39: 1054–1965CrossRefGoogle Scholar
  6. Kawamoto S, Holaka H (1984) l-(5-Iscquinolinesulfcnyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem Biophys Res Comnun 125: 258–261Google Scholar
  7. Maraganore JM (1987) Structural elements for protein-phospholipid interactions may be shared in protein kinase C and phospholipases A2 Trends Biochem Sci 12: 176–177.CrossRefGoogle Scholar
  8. Nishizuka Y (1988) The heterogenicity and differential expression of multiple species of the protein kinase C family. Biofactors 1: 17–20PubMedGoogle Scholar
  9. Zick, Y, Grinberger, G, Rees-Jones, RW, Ccmi R (1985) Use of tyrosine containing polymers to characterize the substrate specificity of insulin and other honnone-stimulated tyrosine kinases. Eur J Biochem 148: 177–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • G. Gat-Yablonski
    • 1
  • R. Sagi-Eisenberg
    • 1
  1. 1.Department of Chemical ImmunologyThe Weizmann Institute of ScienceRehovotIsrael

Personalised recommendations