Abstract
The phorbol diester receptor present in the particulate fraction of rat brain was solubilized by divalent ion chelation in the absence of detergents. The soluble receptor was partially purified by (NH4)2SO4 precipitation, DEAE-cellulose, and gel filtration chromatography. The purified receptor required exogenous phospholipid for activity and displayed a Kd of 7 nM for [3H]phorbol 12, 13-dibutyrate. Biologically active phorbol analogs inhibited binding, whereas inactive analogs did not. The Ca2+-dependent, phospholipid-sensitive protein kinase C copurified with the phorbol receptor. Purified protein kinase C was activated directly by phorbol 12-myristate 13-acetate in the presence of phospholipid.
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Selected References
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- Blumberg P. M., Driedger P. E., Rossow P. W. Effect of a phorbol ester on a transformation-sensitive surface protein of chick fibroblasts. Nature. 1976 Dec 2;264(5585):446–447. doi: 10.1038/264446a0. [DOI] [PubMed] [Google Scholar]
- Cabral F., Gottesman M. M., Yuspa S. H. Induction of specific protein synthesis by phorbol esters in mouse epidermal cell culture. Cancer Res. 1981 Jun;41(6):2025–2031. [PubMed] [Google Scholar]
- Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
- DeChatelet L. R. Initiation of the respiratory burst in human polymorphonuclear neutrophils: a critical review. J Reticuloendothel Soc. 1978 Jul;24(1):73–91. [PubMed] [Google Scholar]
- Driedger P. E., Blumberg P. M. Specific binding of phorbol ester tumor promoters. Proc Natl Acad Sci U S A. 1980 Jan;77(1):567–571. doi: 10.1073/pnas.77.1.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Driedger P. E., Blumberg P. M. The effect of phorbol diesters on chicken embryo fibroblasts. Cancer Res. 1977 Sep;37(9):3257–3265. [PubMed] [Google Scholar]
- Dunphy W. G., Kochenburger R. J., Castagna M., Blumberg P. M. Kinetics and subcellular localization of specific [3H]phorbol 12, 13-dibutyrate binding by mouse brain. Cancer Res. 1981 Jul;41(7):2640–2647. [PubMed] [Google Scholar]
- Fletcher M. P., Gallin J. I. Degranulating stimuli increase the availability of receptors on human neutrophils for the chemoattractant f-met-leu-phe. J Immunol. 1980 Apr;124(4):1585–1588. [PubMed] [Google Scholar]
- Goodwin B. J., Weinberg J. B. Receptor-mediated modulation of human monocyte, neutrophil, lymphocyte, and platelet function by phorbol diesters. J Clin Invest. 1982 Oct;70(4):699–706. doi: 10.1172/JCI110665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamilton J. A., Dientsman S. R. Induction of macrophage DNA synthesis by phorbol esters. J Cell Physiol. 1981 Mar;106(3):445–450. doi: 10.1002/jcp.1041060314. [DOI] [PubMed] [Google Scholar]
- Hergenhahn M., Hecker E. Specific binding of the tumor promoter TPA in various mouse organs as measured by a "cold acetone-filter assay'. Carcinogenesis. 1981;2(12):1277–1281. doi: 10.1093/carcin/2.12.1277. [DOI] [PubMed] [Google Scholar]
- Horowitz A. D., Greenebaum E., Weinstein I. B. Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2315–2319. doi: 10.1073/pnas.78.4.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huberman E., Callaham M. F. Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1293–1297. doi: 10.1073/pnas.76.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huberman E., Weeks C., Herrmann A., Callaham M., Slaga T. Alterations in polyamine levels induced by phorbol diesters and other agents that promote differentiation in human promyelocytic leukemia cells. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1062–1066. doi: 10.1073/pnas.78.2.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koeffler H. P., Bar-Eli M., Territo M. Phorbol diester-induced macrophage differentiation of leukemic blasts from patients with human myelogenous leukemia. J Clin Invest. 1980 Nov;66(5):1101–1108. doi: 10.1172/JCI109939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee L. S., Weinstein I. B. Membrane effects of tumor promoters: stimulation of sugar uptake in mammalian cell cultures. J Cell Physiol. 1979 Jun;99(3):451–460. doi: 10.1002/jcp.1040990319. [DOI] [PubMed] [Google Scholar]
- Lee L. S., Weinstein I. B. Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. Science. 1978 Oct 20;202(4365):313–315. doi: 10.1126/science.308698. [DOI] [PubMed] [Google Scholar]
- Lotem J., Sachs L. Regulation of normal differentiation in mouse and human myeloid leukemic cells by phorbol esters and the mechanism of tumor promotion. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5158–5162. doi: 10.1073/pnas.76.10.5158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minakuchi R., Takai Y., Yu B., Nishizuka Y. Widespread occurrence of calcium-activated, phospholipid-dependent protein kinase in mammalian tissues. J Biochem. 1981 May;89(5):1651–1654. doi: 10.1093/oxfordjournals.jbchem.a133362. [DOI] [PubMed] [Google Scholar]
- Ohuchi K., Levine L. Stimulation of prostaglandin synthesis by tumor-promoting phorbol-12, 13-diesters in canine kidney (MDCK) cells. Cycloheximide inhibits the stimulated prostaglandin synthesis, deacylation of lipids, and morphological changes. J Biol Chem. 1978 Jul 10;253(13):4783–4790. [PubMed] [Google Scholar]
- Pegoraro L., Abrahm J., Cooper R. A., Levis A., Lange B., Meo P., Rovera G. Differentiation of human leukemias in response to 12-0-tetradecanoylphorbol-13-acetate in vitro. Blood. 1980 May;55(5):859–862. [PubMed] [Google Scholar]
- Rovera G., O'Brien T. G., Diamond L. Induction of differentiation in human promyelocytic leukemia cells by tumor promoters. Science. 1979 May 25;204(4395):868–870. doi: 10.1126/science.286421. [DOI] [PubMed] [Google Scholar]
- Shoyab M., De Larco J. E., Todaro G. J. Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature. 1979 May 31;279(5712):387–391. doi: 10.1038/279387a0. [DOI] [PubMed] [Google Scholar]
- Shoyab M., Todaro G. J. Partial purification and characterization of a binding protein for biologically active phorbol and ingenol esters from murine sera. J Biol Chem. 1982 Jan 10;257(1):439–445. [PubMed] [Google Scholar]
- 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]
- Shoyab M., Warren T. C., Todaro G. J. Tissue and species distribution and developmental variation of specific receptors for biologically active phorbol and ingenol esters. Carcinogenesis. 1981;2(12):1273–1276. doi: 10.1093/carcin/2.12.1273. [DOI] [PubMed] [Google Scholar]
- Solanki V., Slaga T. J. Specific binding of phorbol ester tumor promoters to intact primary epidermal cells from Sencar mice. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2549–2553. doi: 10.1073/pnas.78.4.2549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Touraine J. L., Hadden J. W., Touraine F., Hadden E. M., Estensen R., Good R. A. Phorbol myristate acetate: a mitogen selective for a T-lymphocyte subpopulation. J Exp Med. 1977 Feb 1;145(2):460–465. doi: 10.1084/jem.145.2.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wertz P. W., Mueller G. C. Rapid stimulation of phospholipid metabolism in bovine lymphocytes by tumor-promoting phorbol esters. Cancer Res. 1978 Sep;38(9):2900–2904. [PubMed] [Google Scholar]
- White J. G., Estensen R. D. Selective labilization of specific granules in polymorphonuclear leukocytes by phorbol myristate acetate. Am J Pathol. 1974 Apr;75(1):45–60. [PMC free article] [PubMed] [Google Scholar]
- White J. G., Rao G. H., Estensen R. D. Investigation of the release reaction in platelets exposed to phorbol myristate acetate. Am J Pathol. 1974 May;75(2):301–314. [PMC free article] [PubMed] [Google Scholar]
- Wise B. C., Raynor R. L., Kuo J. F. Phospholipid-sensitive Ca2+-dependent protein kinase from heart. I. Purification and general properties. J Biol Chem. 1982 Jul 25;257(14):8481–8488. [PubMed] [Google Scholar]
- Wrenn R. W., Katoh N., Kuo J. F. Stimulation by phospholipid of calcium-dependent phosphorylation of endogenous proteins from mammalian tissues. Biochim Biophys Acta. 1981 Aug 17;676(2):266–269. doi: 10.1016/0304-4165(81)90195-1. [DOI] [PubMed] [Google Scholar]
- Yuspa S. H., Lichti U., Ben T., Patterson E., Hennings H., Slaga T. J., Colburn N., Kelsey W. Phorbol esters stimulate DNA synthesis and ornithine decarboxylase activity in mouse epidermal cell cultures. Nature. 1976 Jul 29;262(5567):402–404. doi: 10.1038/262402a0. [DOI] [PubMed] [Google Scholar]