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Phosphatidylinosito...
Phosphatidylinositol 3-kinase is essential for kit ligand-mediated survival, whereas interleukin-3 and flt3 ligand induce expression of antiapoptotic Bcl-2 family genes
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- Karlsson, Richard (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Kraft, Maria (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Institutionen för translationell medicin,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Department of Translational Medicine
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- Malmberg, Maria (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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Karlberg, P (författare)
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Pronk, CJH (författare)
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- Richter, Johan (författare)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Jönsson, Jan-Ingvar (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2003-11-01
- 2003
- Engelska.
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 74:5, s. 923-931
- Relaterad länk:
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http://dx.doi.org/10...
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https://jlb.onlineli...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cytokines such as interleukin 3 (IL-3), kit ligand (KL), and flt3 ligand (FL) promote survival of hematopoietic stem cells and myeloid progenitor cells. In many cell types, members of the Bcl-2 gene family are major regulators of survival, but the mediating mechanisms are not fully understood. Using two myeloid progenitor cell lines, FDCP-mix and FDC-P1, as well as primary mouse bone marrow progenitors, we demonstrate that KL-mediated survival is dependent on the activation of phosphatidylinositol-3 (PI-3) kinase. The inhibitor LY294002 was able to completely abolish survival mediated by KL, whereas IL-3 and FL were only partially affected. Although all three cytokines induced phosphorylation of protein kinase B (PKB), only KL required PI-3 kinase activity to elicit survival in hematopoietic progenitors. In contrast, pretreatment of cells with inhibitors to the MAP kinase pathway did not affect the survival. We next established if IL-3 and FL activated antiapoptotic Bcl-2 and the related genes Bcl-X-L and Mcl-1. By RNA protection assay and Western blot analysis, we show that all three genes are induced by IL-3, whereas FL induces Bcl-2 and to some extent Bcl-XL. Importantly, KL could not sustain their expression. Moreover, use of inhibitors implied that IL-3 was mainly exerting its effect on Bcl-2 at the level of transcription. The addition of LY294002 did not affect the expression of Bcl-2 and Bcl-XL, and thus, we conclude that expression of antiapoptotic Bcl-2 family member genes is not dependent on PI-3 kinase activity. Our results indicate that cytokines exert distinct survival effects and that FL and IL-3 are capable of sustaining progenitor survival by upregulating the expression of Bcl-2 and related genes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- apoptosis
- cytokines
- hematopoiesis
- progenitor
- bcl-2
- PKB
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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