Home LiteratureArticle Details
PMID: 3265621 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin-3-stimulated haemopoietic stem cell proliferation. Evidence for activation of protein kinase C and Na+/H+ exchange without inositol lipid hydrolysis.

The Biochemical journal ·Vol. 256 ·No. 2 ·1988-12-01 ·Pages 585-92

Whetton AD, Vallance SJ, Monk PN, Cragoe EJ, Dexter TM, Heyworth CM

Abstract

Interleukin 3 (IL-3) is an important regulator of haemopoietic stem cell proliferation both in vivo and in vitro. Little is known about the possible mechanisms whereby this growth factor acts on stem cells to stimulate cell survival and proliferation. Here we have investigated the role of intracellular pH and the Na+/H+ antiport in stem cell proliferation using the multipotential IL-3-dependent stem cell line, FDCP-Mix 1. Evidence is presented that IL-3 can stimulate the activation of an amiloride-sensitive Na+/H+ exchange via protein kinase C activation. IL-3-mediated activation of the Na+/H+ exchange is not observed in FDCP-Mix 1 cells where protein kinase C levels have been down-modulated by treatment with phorbol esters. Also the protein kinase C inhibitor H7 can inhibit IL-3-mediated increases in intracellular pH. This activation of Na+/H+ exchange via protein kinase C has been shown to occur with no measurable effects of IL-3 on inositol lipid hydrolysis or on cytosolic Ca2+ levels. Evidence is also presented that this IL-3-stimulated alkalinization acts as a signal for cellular proliferation in stem cells.

MeSH Terms
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Cell Division/drug effects Cell Line Enzyme Activation Hematopoietic Stem Cells/drug effects Hydrogen-Ion Concentration Inositol Phosphates/metabolism Interleukin-3/pharmacology Isoquinolines/pharmacology Piperazines/pharmacology Protein Kinase C/antagonists & inhibitors,metabolism Tetradecanoylphorbol Acetate/pharmacology Thymidine/metabolism
Chemicals
Inositol Phosphates Interleukin-3 Isoquinolines Piperazines 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Protein Kinase C Tetradecanoylphorbol Acetate Thymidine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Whetton A D
Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology, U.K.
Vallance S J
Monk P N
Cragoe E J
Dexter T M
Heyworth C M
References (37)
37 references, click to expand
  1. Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors.
    Differentiation. 1986;31(2):111-8 PMID: 3091439
  2. Inhibition of chemotactic factor-activated Na+/H+ exchange in human neutrophils by analogues of amiloride: structure-activity relationships in the amiloride series.
    Mol Pharmacol. 1986 Aug;30(2):112-20 PMID: 3016497
  3. Early signals in the mitogenic response.
    Science. 1986 Oct 10;234(4773):161-6 PMID: 3018928
  4. Multilineage hematopoietic growth factor interleukin 3 and direct activators of protein kinase C stimulate phosphorylation of common substrates.
    Blood. 1986 Oct;68(4):906-13 PMID: 3489492
  5. Phorbol esters activate protein kinase C and glucose transport and can replace the requirement for growth factor in interleukin-3-dependent multipotent stem cells.
    J Cell Sci. 1986 Aug;84:93-104 PMID: 3492504
  6. The haemopoietic growth factors interleukin 3 and colony stimulating factor-1 stimulate proliferation but do not induce inositol lipid breakdown in murine bone-marrow-derived macrophages.
    EMBO J. 1986 Dec 1;5(12):3281-6 PMID: 3493133
  7. Insulin increases membrane and cytosolic protein kinase C activity in BC3H-1 myocytes.
    J Biol Chem. 1987 Mar 15;262(8):3633-9 PMID: 3546313
  8. Metabolic effects of interleukin 3 on 32D cl23 cells analyzed by NMR.
    J Cell Physiol. 1987 Nov;133(2):351-7 PMID: 3500178
  9. Signal transduction through the EGF receptor transfected in IL-3-dependent hematopoietic cells.
    Science. 1988 Feb 5;239(4840):628-31 PMID: 3257584
  10. Interleukin 3-specific tyrosine phosphorylation of a membrane glycoprotein of Mr 150,000 in multi-factor-dependent myeloid cell lines.
    EMBO J. 1987 Dec 20;6(13):3979-84 PMID: 3502088
  11. Interleukin 3 stimulates proliferation via protein kinase C activation without increasing inositol lipid turnover.
    Proc Natl Acad Sci U S A. 1988 May;85(10):3284-8 PMID: 3259317
  12. Mitogenic effect of alkaline pH on quiescent, serum-starved cells.
    Proc Natl Acad Sci U S A. 1981 Jul;78(7):4334-8 PMID: 6945587
  13. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator.
    J Cell Biol. 1982 Aug;94(2):325-34 PMID: 6980885
  14. Cytoplasmic pH and free Mg2+ in lymphocytes.
    J Cell Biol. 1982 Oct;95(1):189-96 PMID: 6815204
  15. Effect of haematopoietic cell growth factor on intracellular ATP levels.
    Nature. 1983 Jun 16-22;303(5918):629-31 PMID: 6855907
  16. Characterization and partial purification of a haemopoietic cell growth factor in WEHI-3 cell conditioned medium.
    Biochem J. 1983 Mar 15;210(3):747-59 PMID: 6575777
  17. Na+/H+ exchange and cytoplasmic pH in the action of growth factors in human fibroblasts.
    Nature. 1983 Aug 18-24;304(5927):645-8 PMID: 6410286
  18. Blockade of the Na+/H+ antiport abolishes growth factor-induced DNA synthesis in fibroblasts. Structure-activity relationships in the amiloride series.
    J Biol Chem. 1984 Apr 10;259(7):4313-9 PMID: 6323465
  19. Haemopoietic cell growth factor mediates cell survival via its action on glucose transport.
    EMBO J. 1984 Feb;3(2):409-13 PMID: 6370682
  20. The role of protein kinase C in cell surface signal transduction and tumour promotion.
    Nature. 1984 Apr 19-25;308(5961):693-8 PMID: 6232463
  21. Inositol trisphosphate and diacylglycerol as second messengers.
    Biochem J. 1984 Jun 1;220(2):345-60 PMID: 6146314
  22. Haemopoietic cell growth factor and glucose transport. Its role in cell survival and the relevance of this in normal haemopoiesis and leukaemia.
    Differentiation. 1984;27(3):163-7 PMID: 6389247
  23. A common sequence of calcium and pH signals in the mitogenic stimulation of eukaryotic cells.
    Nature. 1985 Feb 7-13;313(6002):481-4 PMID: 3918272
  24. Role of a Na+-dependent Cl-/HCO3- exchange in regulation of intracellular pH in fibroblasts.
    J Biol Chem. 1985 Apr 25;260(8):4877-83 PMID: 2985569
  25. Altered cytosol/membrane enzyme redistribution on interleukin-3 activation of protein kinase C.
    Nature. 1985 May 16-22;315(6016):235-7 PMID: 3158821
  26. Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism.
    Cell. 1985 Jul;41(3):677-83 PMID: 2988782
  27. Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism.
    Cell. 1985 Jul;41(3):685-93 PMID: 2988783
  28. The granulocyte-macrophage colony-stimulating factors.
    Science. 1985 Jul 5;229(4708):16-22 PMID: 2990035
  29. Stimulation of Na+/H+ antiport activity by epidermal growth factor and insulin occurs without activation of protein kinase C.
    Biochem Biophys Res Commun. 1985 Jul 31;130(2):646-53 PMID: 2992479
  30. Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes.
    Nature. 1985 Oct 3-9;317(6036):434-8 PMID: 3930972
  31. Hierarchical down-modulation of hemopoietic growth factor receptors.
    Cell. 1985 Nov;43(1):269-76 PMID: 3000602
  32. Stimulation of hematopoiesis in vivo by recombinant bacterial murine interleukin 3.
    Proc Natl Acad Sci U S A. 1986 Feb;83(4):1001-5 PMID: 3081887
  33. The kinetic response of haemopoietic precursor cells, in vivo, to highly purified, recombinant interleukin-3.
    Lymphokine Res. 1986 Spring;5(2):97-104 PMID: 3084879
  34. Effects of growth factors on intracellular pH regulation.
    Annu Rev Physiol. 1986;48:363-76 PMID: 3010817
  35. Protein kinase C activation by diacylglycerol second messengers.
    Cell. 1986 Jun 6;45(5):631-2 PMID: 3708690
  36. Identification of the interleukin-3 receptor using an iodinatable, cleavable, photoreactive cross-linking agent.
    J Biol Chem. 1986 Jul 15;261(20):9094-7 PMID: 3087986
  37. Identification of distinct receptors for two hemopoietic growth factors (granulocyte colony-stimulating factor and multipotential colony-stimulating factor) by chemical cross-linking.
    J Biol Chem. 1986 Sep 15;261(26):12384-9 PMID: 3017972
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2560585
Published
1988-12-01
Pages
585-92
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1135450
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2560585 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2