Conventional protein kinase C isoforms are not essential for cellular proliferation of a T cell lymphoma line.
The role of conventional protein kinase C (PKC) isoforms in the proliferation of a T cell lymphoma line was investigated, PKC isozyme-deficient cell lines were generated from HuT 78 which expresses PKC isoforms alpha, beta, epsilon and zeta. The first of these, K-4, expresses PKC alpha, epsilon and zeta but not beta. L-2, a mutant of K-4, expresses PKC alpha and zeta but expresses neither PKC alpha, beta, gamma, epsilon nor zeta when cultured continuously in PMA (L-2/PMA). All four cell lines continued to proliferate although at reduced rates in the presence of the PKC inhibitors staurosporine and H-7. K-4 and HuT 78 undergo growth arrest when activated with PMA (rate of proliferation decreases by 76 and 95%, respectively). While PMA-induced growth arrest occurs in L-2 cells which possess PKC alpha and zeta, PMA-induced growth arrest does not occur in L-2/PMA which is deficient in these isoforms. As these cell lines continue to proliferate in the presence of PKC inhibitors and since proliferation occurs in the absence of PKC isoforms (L-2/PMA), the results suggest that neither conventional PKC nor the epsilon and zeta isoforms are essential for proliferation of these cells. These data further suggest that PKC alpha and/or zeta may be involved in PMA-induced growth arrest.
Long
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Department of Clinical Medicine, Trinity College Dublin, St. James's Hospital, Ireland.
Kelleher
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007527:Isoenzymes; D007546:Isoquinolines; D010879:Piperazines; D014316:Tritium; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine