Phosphatidylinositol Hydrolysis and an Increase in Ca2+ Concentration in the Signal-Transduction Process Triggered by Murine FcgammaRIII are not Required for Protein Kinase C Translocation

Abstract

Murine class I11 receptors for IgG (mFcyRII1) are composed of an IgG-binding a chain associated with a y subunit dimer. These receptors have been shown to trigger the release of serotonin and tumor necrosis factor-a [Daeron, M., Latour, S., Hiickel, C., Bonnerot, C Zmmunol. 152,. Using a transfection model where the cDNA encoding mFcyRIII was stably transfected into the rat basophilic leukemia cell line RBL-2H3, we found that the functional efficiency of mFcyRIII is correlated with its ability to increase the intracellular Ca2+ concentration and to stimulate inositol phosphate metabolism.The deletion of intracellular sequences of the a subunit did not alter the ability of mFcyRII1 to trigger the Ca2+ and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] response. After substitution of the intracellular domain of mFcyRII for that of mFcyRIIIy, but not that of mFcyRIIIa, the chimeric receptor was also able to trigger Caz+ and PtdIns(4,5)P2 responses.In contrast, all transfected receptors induced protein kinase C translocation. Furthermore, dimerization of the receptor was sufficient for the initiation of this protein kinase C translocation while a further crosslinking was necessary for the induction of the Ca2+ and PtdIns(4,5)P2 responses.Protein kinase C translocation therefore can be dissociated from Ca2+ mobilization, PtdIns(4,5)P2 turnover and mast cell secretory responses induced by murine FcyRIII.