Role of a guanine nucleotide-binding regulatory protein in the hydrolysis of phosphatidylinositol 4,5-bisphosphate in a human T cell line.
The CD3(T3)/antigen receptor complex appears to function by transducing an antigen signal presented by macrophages into the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. In order to find out how the CD3/antigen receptor complex regulates the hydrolysis of PtdIns(4,5)P2 to diacylglycerol and inositol trisphosphate, we investigated the possible role played by a guanine nucleotide-binding regulatory protein in PtdIns(4,5)P2 hydrolysis in a human T cell leukemia line, JURKAT. JURKAT cells were made permeable to Al3+, F-, GTP, and a nonhydrolyzable GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), by treatment with pseudomonal cytotoxin. In the presence of AlCl3 NaF stimulated the release of inositol phosphates in the cytotoxin-treated JURKAT cells. NaF plus AlCl3 induced increases in inositol tris-, bis-, and mono-phosphates and decreases in PtdIns(4,5)P2, phosphatidylinositol 4-phosphate, and phosphatidylinositol within 5 min after addition to the cytotoxin-treated cells at 37 C. GTP gamma S stimulated, to some extent, polyphosphoinositide hydrolysis in the cytotoxin-treated JURKAT. The cytotoxin-treated JURKAT cells retained the ability to respond to anti-Leu-4 with polyphosphoinositide hydrolysis. It has been shown that Al3+ in the presence of F- modulates the activity of various guanine nucleotide-binding regulatory proteins. Therefore, the results obtained in this study indicate that a guanine nucleotide-binding regulatory protein regulates the polyphosphoinositide breakdown in JURKAT cells by influencing phosphodiesterase activity.
Hasegawa-Sasaki
H
H
Department of Biochemistry, Sapporo Medical College.
Lutz
F
F
Sasaki
T
T
D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D007938:Leukemia; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D013601:T-Lymphocytes; D014316:Tritium
D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D014316:Tritium; D019204:GTP-Binding Proteins