Tyrosine kinase but not phospholipid/Ca2+ signaling pathway is involved in interferon-gamma stimulation of Ia expression in macrophages.
The specific signal transduction pathway(s) involved in the induction of the expression of the MHC class II molecule, Ia, on macrophages by interferon-gamma (IFN-gamma) is unclear. In this paper, we assessed the role of several signal transduction pathways including calcium mobilization, phospholipase C, protein kinase C and cyclic nucleotide-dependent protein kinase, and the tyrosine kinase pathways. IFN-gamma was unable to mobilize intracellular calcium, unlike platelet-activating factor, which stimulated a threefold increase in cytosolic Ca2+ concentration in macrophages. Inhibition of the phospholipase C pathway by U73122 or ET-180CH3 and of phosphatidic acid phosphohydrolase by propranolol did not suppress IFN-gamma-induced Ia expression. In addition, inhibition of protein kinase C by calphostin C or cyclic nucleotide-dependent protein kinase by HA1004 did not suppress Ia expression. However, IFN-gamma-induced Ia expression was significantly suppressed when the tyrosine kinase pathway was inhibited with herbimycin A and genestein. In addition, those two inhibitors suppressed tyrosine phosphorylation of several proteins in macrophages that may or may not be involved in the induction of Ia expression. Thus, IFN-gamma used only the tyrosine kinase signaling pathway, but not the phospholipid/Ca2+ signaling pathways, to induce Ia expression in macrophages.
Chakrabarti
R
R
Department of Cell Biology and Human Anatomy, University of California, School of Medicine, Davis 95616-8643, USA.
Erickson
K L
KL
D000818:Animals; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010716:Phosphatidylinositols / Q000502:physiology; D010739:Phospholipase D / Q000502:physiology; D010743:Phospholipids / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D013268:Stimulation, Chemical
D004791:Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; D010716:Phosphatidylinositols; D010743:Phospholipids; D047428:Protein Kinase Inhibitors; D007371:Interferon-gamma; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D010739:Phospholipase D; D002118:Calcium