PHORBOL ESTER-INDUCED TRANSCRIPTION OF AN IMMEDIATE-EARLY RESPONSE GENE BY HUMAN T-CELLS IS INHIBITED BY CO-TREATMENT WITH CALCIUM IONOPHORE

Human T cells require two discrete signals to initiate their prolifera tion. In jurkat T cells the first signal can be provided by the phorbo l ester TPA and the second by the calcium ionophore A23187. We have is olated a cDNA from Jurkat T cells representing mRNA induced by TPA but inhibited by simultaneous treatment of the cells with antibody, lecti n, or A23187. Sequencing revealed identity of the Jurkat clone to a cD NA, termed ETR101, recently isolated from HL60 promyelocytic leukaemia cells and shown to be an immediate early gene expressed upon TPA stim ulation of these cells [Shimizu et al.:J Biol Chem 266:12157, 1991]. T he gene is also induced very rapidly upon TPA treatment of Jurkat cell s and is superinduced by co-treatment with cycloheximide. The predicte d amino acid sequence encoded by ETR101 has weak homology to junB and JunD, therefore it is of some interest that these three genes share th e chromosomal localization, 19p13.2. The divergent effects of TPA trea tment upon cell proliferation and differentiation in different circums tances allow some speculation about a possible role for the ETR101 gen e product upon cellular differentiation. (C) 1994 Wiley-Liss, Inc.