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

Abstract

Murine class III receptors for IgG (mFc gamma RIII) are composed of an IgG-binding alpha chain associated with a gamma subunit dimer. These receptors have been shown to trigger the release of serotonin and tumor necrosis factor-alpha [Daëron, M., Latour, S., Hückel, C., Bonnerot, C. & Fridman, W. H. (1992) Immunobiology 185, 159-174], and are involved in endocytosis and phagocytosis [Daëron, M., Malbec, O., Bonnerot, C., Latour, S., Segal, D. M. & Fridman, W. H. (1994) J. Immunol. 152, 783-792]. Using a transfection model where the cDNA encoding mFc gamma RIII was stably transfected into the rat basophilic leukemia cell line RBL-2H3, we found that the functional efficiency of mFc gamma RIII is correlated with its ability to increase the intracellular Ca2+ concentration and to stimulate inositol phosphate metabolism. The deletion of intracellular sequences of the alpha subunit did not alter the ability of mFc gamma RIII to trigger the Ca2+ and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] response. After substitution of the intracellular domain of mFc gamma RIII for that of mFc gamma RIII gamma, but not that of mFc gamma RIII alpha, the chimeric receptor was also able to trigger Ca2+ 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 Fc gamma RIII.

Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor

“…CD64 is known to regulate CD32B activation in leukocytes (37). Our study implicates CD64 in regulating a neural protein's surface expression.…”

Induction of Phagocytosis and Intracellular Signaling by an Inhibitory Channel Catfish Leukocyte Immune-Type Receptor: Evidence for Immunoregulatory Receptor Functional Plasticity in Teleosts

“…One possible explanation for this observation is that IpLITR 1.1b employs a Ca 2+ -independent signaling mechanism to control phagocytosis. IgG-mediated phagocytosis in human neutrophils can also be Ca 2+ independent [44], and in fact protein kinase C translocation to the plasma membrane is known to be Ca 2+ independent in RBL-2H3 cells [45]. Alternatively, human monocytes utilize a Ca 2+ -independent phagocytic phospholipase/phospholipase A 2 to carry out IgG-mediated phagocytosis [46].…”

The Inhibitory Mechanism of Rebamipide on the Mediator Release in the Guinea Pig Lung Mast Cells Activated with Specific Antigen-Antibody Reactions

“…The precipitated proteins were filtered through a glass fiber disk to eliminate unreacted [Á-32 P]ATP, washed 4 times with 20 mmol/l tetra-sodium pyrophosphate and once with absolute ethanol. After the glass fiber disks were dried, radioactivities were measured with a liquid scintillation counter [43].…”