Antagonistic effects of calcium ionophores and phorbol esters on T cell receptor mRNA levels in human thymocytes.
Levels of mRNA of the T cell antigen receptors (TcR) in human thymocytes are differentially regulated in response to distinct intracellular signals. Activation of protein kinase C by the phorbol ester, tetradecanoyl phorbol acetate or other phorbol esters increases the levels of the alpha and beta T cell receptor (TcR-alpha, TcR-beta) mRNA, whereas an increase in cytosolic free Ca2+, induced by ionomycin or other Ca2+ ionophores, results in a decrease of alpha and beta TcR mRNA levels. In contrast, ionomycin increases the expression TcR-gamma mRNA whereas tetradecanoyl phorbol acetate prevents this induction. Our results suggest the existence of two opposing intracellular pathways that control expression of TcR-alpha and TcR-beta mRNA levels, on the one hand and TcR-gamma mRNA, on the other. These results provide the first evidence for antagonistic actions of protein kinase C and cytosolic-free Ca2+ on gene expression.
Martinez-Valdez
H
H
Division of Immunology/Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
Doherty
P J
PJ
Thompson
E
E
Benedict
S H
SH
Gelfand
E W
EW
Cohen
A
A
D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004987:Ethers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015759:Ionomycin; D007476:Ionophores / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004987:Ethers; D007476:Ionophores; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium