Evidence for posttranscriptional regulation of transgenic protein kinase C-alpha in T cells.
Recently, we succeeded in establishing a transgenic mouse line which expressed high levels of protein kinase C (PKC)-alpha in thymocytes at the mRNA level with disproportionately small increases at the protein level. The transgenic PKC-alpha was nevertheless functionally active for inducing accelerated cell growth and IL-2 production by stimulation with anti-receptor (CD3) antibody or phorbol 12-myristate 14-acetate (PMA) in vitro. Study of the dynamics of transgenic PKC-alpha in the cells in vitro showed that the amount of PKC-alpha protein increased in the cells remarkably at > or = 5 h after stimulation, whereas the level of PKC-alpha mRNA did not change significantly or changed slightly. This suggested that cell activation breaks the posttranscriptional regulation of the transgenic PKC-alpha in resting cells. The increase in PKC-alpha protein accompanied a prolonged membrane translocation of PKC-alpha and enhanced cell proliferation. Such a transgenic effect was inhibited completely by a PKC inhibitor, H-7, added during 0-6 h after the stimulation. These results show formally that the transgenic PKC-alpha whose production was accelerated through cell activation plays a key role in the late (for > or = 5 h) signal delivery for disregulated cell growth.
Iwamoto
T
T
Department of Immunology, Nagoya University School of Medicine, Japan.
Ohkusu
K
K
Watanabe
M
M
Hidaka
H
H
Nakashima
I
I
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic
D000906:Antibodies; D017252:CD3 Complex; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate