PMID:9013981

Citation	Shinji, H, Akagawa, KS, Tsuji, M, Maeda, M, Yamada, R, Matsuura, K, Yamamoto, S and Yoshida, T (1997) Lipopolysaccharide-induced biphasic inositol 1,4,5-trisphosphate response and tyrosine phosphorylation of 140-kilodalton protein in mouse peritoneal macrophages. J. Immunol. 158:1370-6
Abstract	We previously showed that a relatively high dose of LPS induced the selective translocation of protein kinase C-beta (PKC-beta) in LPS-responsive mouse macrophages. This result suggested that phosphatidylinositol-specific phospholipase C (PLC) might be activated in the upstream of PKC-beta. Stimulation of C3H/HeN mouse macrophages by LPS induced the characteristic phosphatidylinositol-1,4,5-trisphosphate (IP3) response, that is, a biphasic response consisting of a rapid increase occurring within the first 1 min, and another increase beginning at around 1 min after stimulation. Only the first response was disappeared when cells were treated with a platelet-activating factor receptor antagonist. LPS-inducible TNF-alpha gene activation, however, was not suppressed by the same antagonist, but suppressed by PKC inhibitors. LPS-stimulated macrophage lysates showed tyrosine phosphorylation of some proteins, and the strongest phosphorylation was observed at molecular mass of 140 kDa. The phosphorylation of this protein started at 40 s after LPS stimulation and continued to increase. Anti-PLC-gamma2 Ab seemed to recognize the same protein as the tyrosine-phosphorylated 140-kDa protein. A low dose of LPS (1 ng/ml) could not induce the tyrosine phosphorylation of this protein. Furthermore, LPS induced only the first phase change, but not the second phase increase in LPS-hyporesponsive C3H/HeJ mouse macrophages. These results indicate that the first phase rapid IP3 change, which is also seen in HeJ macrophages, is mediated via a platelet-activating factor receptor, and is not responsible for TNF-alpha production, while the second phase change mediated by a molecule other than CD14 is responsible for PKC-beta translocation and TNF-alpha production. The results also suggest that the later IP3 change is considered to be mediated through a gamma2 type of phosphatidylinositol-specific PLC.
Links	PubMed
Keywords	Animals; Benzoquinones; Dose-Response Relationship, Drug; Inositol 1,4,5-Trisphosphate/metabolism; Isoenzymes/metabolism; Lactams, Macrocyclic; Lipopolysaccharides/pharmacology; Macrophages, Peritoneal/metabolism; Male; Mice; Mice, Inbred C3H; Molecular Weight; Phospholipase C gamma; Phosphoproteins/metabolism; Phosphotyrosine/metabolism; Platelet Membrane Glycoproteins/antagonists & inhibitors; Platelet Membrane Glycoproteins/physiology; Protein-Tyrosine Kinases/antagonists & inhibitors; Quinones/pharmacology; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction; Type C Phospholipases/metabolism
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