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. 1989 Jul;60(1):15–19. doi: 10.1038/bjc.1989.211

Activation of protein kinase C induces differentiation in the human T-lymphoblastic cell line MOLT-3.

Y Yamauchi 1, K Nagasawa 1, T Mayumi 1, T Horiuchi 1, Y Niho 1
PMCID: PMC2247330  PMID: 2803911

Abstract

We attempted to determine whether or not activation of calcium phospholipid-dependent protein kinase C (PKC) is associated with the induction of differentiation by 12-O-tetradecanoylphorbol-13-acetate (TPA) in the human T-lymphoblastic cell line MOLT-3. PKC activities were assayed in MOLT-3 and its five subclones resistant to TPA-induced cell differentiation. The cytosolic PKC activities of TPA-resistant subclones were 36-53% of that of the parental MOLT-3 cells. TPA treatment led to a rapid decrease in PKC activities in the cytosol, together with a concomitant increase in PKC activities in the particulate fraction, in both MOLT-3 and a TPA-resistant subclone. Thus, translocation of PKC from the cytosol to the membrane occurred following treatment with TPA, in both cell lines. However, the amount of PKC translocated from the cytosol to particulate fraction for 60 min in a TPA-resistant subclone was about 20% of that of the parental MOLT-3 cells. These findings suggest that the quantity of cytosolic PKC activity and the extent of translocation may relate to responses to TPA-induced cell differentiation in this T-cell line.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson N. L., Gemmell M. A., Coussens P. M., Murao S., Huberman E. Specific protein phosphorylation in human promyelocytic HL-60 leukemia cells susceptible or resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate. Cancer Res. 1985 Oct;45(10):4955–4962. [PubMed] [Google Scholar]
  2. Ashendel C. L., Staller J. M., Boutwell R. K. Protein kinase activity associated with a phorbol ester receptor purified from mouse brain. Cancer Res. 1983 Sep;43(9):4333–4337. [PubMed] [Google Scholar]
  3. Ballester R., Rosen O. M. Fate of immunoprecipitable protein kinase C in GH3 cells treated with phorbol 12-myristate 13-acetate. J Biol Chem. 1985 Dec 5;260(28):15194–15199. [PubMed] [Google Scholar]
  4. Bollum F. J. Terminal deoxynucleotidyl transferase as a hematopoietic cell marker. Blood. 1979 Dec;54(6):1203–1215. [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Diamond L., O'Brien T. G., Baird W. M. Tumor promoters and the mechanism of tumor promotion. Adv Cancer Res. 1980;32:1–74. doi: 10.1016/s0065-230x(08)60360-7. [DOI] [PubMed] [Google Scholar]
  7. Homma Y., Henning-Chubb C. B., Huberman E. Translocation of protein kinase C in human leukemia cells susceptible or resistant to differentiation induced by phorbol 12-myristate 13-acetate. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7316–7319. doi: 10.1073/pnas.83.19.7316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Isakov N., Mally M. I., Scholz W., Altman A. T-lymphocyte activation: the role of protein kinase C and the bifurcating inositol phospholipid signal transduction pathway. Immunol Rev. 1987 Feb;95:89–111. doi: 10.1111/j.1600-065x.1987.tb00501.x. [DOI] [PubMed] [Google Scholar]
  9. Kaibuchi K., Takai Y., Sawamura M., Hoshijima M., Fujikura T., Nishizuka Y. Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation. J Biol Chem. 1983 Jun 10;258(11):6701–6704. [PubMed] [Google Scholar]
  10. Kajikawa N., Kaibuchi K., Matsubara T., Kikkawa U., Takai Y., Nishizuka Y., Itoh K., Tomioka C. A possible role of protein kinase C in signal-induced lysosomal enzyme release. Biochem Biophys Res Commun. 1983 Oct 31;116(2):743–750. doi: 10.1016/0006-291x(83)90587-9. [DOI] [PubMed] [Google Scholar]
  11. Kikkawa U., Takai Y., Minakuchi R., Inohara S., Nishizuka Y. Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties. J Biol Chem. 1982 Nov 25;257(22):13341–13348. [PubMed] [Google Scholar]
  12. Kraft A. S., Anderson W. B., Cooper H. L., Sando J. J. Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. J Biol Chem. 1982 Nov 25;257(22):13193–13196. [PubMed] [Google Scholar]
  13. Kraft A. S., Anderson W. B. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 1983 Feb 17;301(5901):621–623. doi: 10.1038/301621a0. [DOI] [PubMed] [Google Scholar]
  14. Kreutter D., Caldwell A. B., Morin M. J. Dissociation of protein kinase C activation from phorbol ester-induced maturation of HL-60 leukemia cells. J Biol Chem. 1985 May 25;260(10):5979–5984. [PubMed] [Google Scholar]
  15. Malaisse W. J., Lebrun P., Herchuelz A., Sener A., Malaisse-Lagae F. Synergistic effect of a tumor-promoting phorbol ester and a hypoglycemic sulfonylurea upon insulin release. Endocrinology. 1983 Nov;113(5):1870–1877. doi: 10.1210/endo-113-5-1870. [DOI] [PubMed] [Google Scholar]
  16. Manger B., Weiss A., Imboden J., Laing T., Stobo J. D. The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex. Effects of stimulation with soluble or immobilized CD3 antibodies. J Immunol. 1987 Oct 15;139(8):2755–2760. [PubMed] [Google Scholar]
  17. Mayumi T., Nagasawa K., Horiuchi T., Kusaba T. Phorbol ester receptors and the induction of differentiation in the human T lymphoblastic cell line MOLT-3. Exp Cell Biol. 1988;56(1-2):12–19. doi: 10.1159/000163458. [DOI] [PubMed] [Google Scholar]
  18. Nagasawa K., Chechik B. E., Gelfand E. W., Sengupta S., Letarte M., Mak T. W. Modulation of human T-cell differentiation markers by 12-O-tetradecanoylphorbol-13-acetate. Thymus. 1981 Nov;3(4-5):307–318. [PubMed] [Google Scholar]
  19. Nagasawa K., Howatson A., Mak T. W. Induction of human malignant T-lymphoblastic cell lines MOLT-3 and jurkat by 12-O-tetradecanoylphorbol-13-acetate: biochemical, physical, and morphological characterization. J Cell Physiol. 1981 Oct;109(1):181–192. doi: 10.1002/jcp.1041090120. [DOI] [PubMed] [Google Scholar]
  20. Nagasawa K., Mak T. W. Phorbol esters induce differentiation in human malignant T lymphoblasts. Proc Natl Acad Sci U S A. 1980 May;77(5):2964–2968. doi: 10.1073/pnas.77.5.2964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  22. Okamura S., Crane F., Messner H. A., Mak T. W. Purification of terminal deoxynucleotidyltransferase by oligonucleotide affinity chromatography. J Biol Chem. 1978 Jun 10;253(11):3765–3767. [PubMed] [Google Scholar]
  23. Parker P. J., Stabel S., Waterfield M. D. Purification to homogeneity of protein kinase C from bovine brain--identity with the phorbol ester receptor. EMBO J. 1984 May;3(5):953–959. doi: 10.1002/j.1460-2075.1984.tb01913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rozengurt E., Rodriguez-Pena A., Coombs M., Sinnett-Smith J. Diacylglycerol stimulates DNA synthesis and cell division in mouse 3T3 cells: role of Ca2+-sensitive phospholipid-dependent protein kinase. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5748–5752. doi: 10.1073/pnas.81.18.5748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sando J. J., Young M. C. Identification of high-affinity phorbol ester receptor in cytosol of EL4 thymoma cells: requirement for calcium, magnesium, and phospholipids. Proc Natl Acad Sci U S A. 1983 May;80(9):2642–2646. doi: 10.1073/pnas.80.9.2642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sharkey N. A., Leach K. L., Blumberg P. M. Competitive inhibition by diacylglycerol of specific phorbol ester binding. Proc Natl Acad Sci U S A. 1984 Jan;81(2):607–610. doi: 10.1073/pnas.81.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shoji M., Girard P. R., Charp P. A., Koeffler H. P., Vogler W. R., Kuo J. F. Effects of phorbol ester on translocation and down-regulation of protein kinase C and phosphorylation of endogenous proteins in human acute myeloid leukemia cell line KG-1 and its phorbol ester-resistant subline KG-1a. Cancer Res. 1987 Dec 1;47(23):6363–6370. [PubMed] [Google Scholar]
  28. Shoyab M., Todaro G. J. Specific high affinity cell membrane receptors for biologically active phorbol and ingenol esters. Nature. 1980 Dec 4;288(5790):451–455. doi: 10.1038/288451a0. [DOI] [PubMed] [Google Scholar]
  29. Solanki V., Slaga T. J., Callaham M., Huberman E. Down regulation of specific binding of [20-3H]phorbol 12,13-dibutyrate and phorbol ester-induced differentiation of human promyelocytic leukemia cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1722–1725. doi: 10.1073/pnas.78.3.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vandenbark G. R., Kuhn L. J., Niedel J. E. Possible mechanism of phorbol diester-induced maturation of human promyelocytic leukemia cells. J Clin Invest. 1984 Feb;73(2):448–457. doi: 10.1172/JCI111231. [DOI] [PMC free article] [PubMed] [Google Scholar]

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