Phosphatidylinositol hydrolysis and an increase in Ca2+ concentration in the signal-transduction process triggered by murine Fc gamma RIII are not required for protein kinase C translocation.
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.
Altrichter
J
J
Institut für Medizinische Biochemie, Universität Rostock, Germany.
Guse
A H
AH
Resch
K
K
Brock
J
J
Daëron
M
M
Hückel
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D010716:Phosphatidylinositols; D017452:Receptors, IgG; D011493:Protein Kinase C; D002118:Calcium