Phorbol esters activate protein kinase C and glucose transport and can replace the requirement for growth factor in interleukin-3-dependent multipotent stem cells.
AffiliationUniversity of Manchester Institute of Science and Technology, Department of Biochemistry and Applied Molecular Biology, P.O. Box 88, Sackville Street, Manchester M60 1QD, UK
MetadataShow full item record
AbstractInterleukin 3 (IL-3) promotes the survival, proliferation and development of progenitor cells from several distinct haemopoietic lineages and can also stimulate the self-renewal of stem cells. We have explored the mode of action of this growth factor in promoting survival and proliferation, using a multipotent haemopoietic stem cell line FDC-Mix 1. In the absence of IL-3 these cells died within 16-48 h. However, this requirement for IL-3 could be replaced by 12-O-tetradecanoylphorbol-13-acetate (TPA) plus Ca2+ ionophore, which promoted not only survival but also DNA synthesis with no concomitant loss of the multipotential nature of these cells. TPA and Ca2+ ionophore, respectively, could also interact synergistically with IL-3 to promote DNA synthesis. Both IL-3 and TPA stimulated the translocation of protein kinase C (PK-C) from the cytosol to a membrane-bound form in FDC-Mix 1 cells. Previously we suggested that IL-3 can activate the primary metabolism of IL-3-dependent cells so that increased glucose transport and glycolysis lead to maintenance of ATP levels and cellular survival. To investigate whether TPA and, or, Ca2+ ionophore could also influence cellular survival via an activation of glucose uptake we assessed the effects of these agents on hexose transport. TPA +/- Ca2+ ionophore activated hexose transport to the same degree as does IL-3 but these agents cannot superstimulate FDC-Mix 1 hexose transport in cells that already exhibit an activated transport system from preincubation with IL-3. We conclude that IL-3 maintains FDC-Mix 1 cells via its ability to activate PK-C and increase cytosolic levels of Ca2+, and that an IL-3-mediated activation of PK-C may promote cellular survival via its ability to enhance hexose uptake by phosphorylating the glucose transport protein.
CitationPhorbol esters activate protein kinase C and glucose transport and can replace the requirement for growth factor in interleukin-3-dependent multipotent stem cells. 1986, 84:93-104 J Cell Sci
JournalJournal of Cell Science
- Interleukin-3-stimulated haemopoietic stem cell proliferation. Evidence for activation of protein kinase C and Na+/H+ exchange without inositol lipid hydrolysis.
- Authors: Whetton AD, Vallance SJ, Monk PN, Cragoe EJ, Dexter TM, Heyworth CM
- Issue date: 1988 Dec 1
- Interleukin 3 stimulates proliferation via protein kinase C activation without increasing inositol lipid turnover.
- Authors: Whetton AD, Monk PN, Consalvey SD, Huang SJ, Dexter TM, Downes CP
- Issue date: 1988 May
- Tumor-promoting phorbol esters stimulate the proliferation of interleukin-3 dependent cells.
- Authors: Hogans BB, Spivak JL
- Issue date: 1988 Nov
- Tumor promoters in conjunction with calcium ionophores mimic antigenic stimulation by reactivation of alloantigen-primed murine T lymphocytes.
- Authors: Isakov N, Altman A
- Issue date: 1985 Dec
- Calcium ionophore but not phorbol ester promotes eicosanoids release by proliferating interleukin-3-dependent bone marrow cells.
- Authors: Shibata Y, McCaffrey PG, Sato H, Oghiso Y
- Issue date: 1990 Oct 15