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Evidence for posttranscriptional regulation of transgenic protein kinase C–alpha in T cells
Author(s) -
Iwamoto Takashi,
Ohkusu Kozo,
Nakashima Izumi,
Watanabe Masato,
Hidaka Hiroyoshi
Publication year - 1994
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240550213
Subject(s) - protein kinase c , transgene , pkc alpha , biology , microbiology and biotechnology , alpha (finance) , stimulation , phorbol , genetically modified mouse , protein kinase a , signal transduction , cell culture , kinase , biochemistry , endocrinology , gene , medicine , construct validity , nursing , genetics , patient satisfaction
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 ⩾ 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 ⩾ 5 h) signal delivery for disregulated cell growth. © 1994 Wiley‐Liss, Inc.