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Activation of the M...
Activation of the MAP kinase pathway by c-Kit is PI-3 kinase dependent in hematopoietic progenitor/stem cell lines
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- Wandzioch, Ewa (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Edling, Charlotte E (author)
- Umeå universitet,Patologi
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Palmer, Ruth H (author)
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- Carlsson, Leif (author)
- Umeå universitet,Umeå centrum för molekylär medicin (UCMM)
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- Hallberg, Bengt (author)
- Umeå universitet,Patologi
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(creator_code:org_t)
- American Society of Hematology, 2004
- 2004
- English.
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:1, s. 51-57
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The Steel factor (SF) and its receptor c-Kit play a critical role for various cell types at different levels in the hematopoietic hierarchy. Whether similar or distinct signaling pathways are used upon c-Kit activation in different cell types within the hematopoietic hierarchy is not known. To study c-Kit signaling pathways in the hematopoietic system we have compared c-Kit downstream signaling events in SF-dependent hematopoietic stem cell (HSC)–like cell lines to those of mast cells. Both Erk and protein kinase B (PKB)/Akt are activated by ligand-induced activation of the c-Kit receptor in the HSC-like cell lines. Surprisingly, phosphoinositide-3 (PI-3) kinase inhibitors block not only PKB/Akt activation but also activation of Raf and Erk. SF-induced activation of Ras is not affected by inhibition of PI-3 kinase. In mast cells and other more committed hematopoietic precursors, the activation of Erk by SF is not PI-3 kinase dependent. Our results suggest that a molecular signaling switch occurs during differentiation in the hematopoietic system whereby immature hematopoietic progenitor/stem cells use a PI-3 kinase–sensitive pathway in the activation of both Erk and PKB/Akt, which is then switched upon differentiation to the more commonly described PI-3 kinase–independent mitogen-activated protein (MAP) kinase pathway.
Keyword
- 1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors/*metabolism
- Animals
- Cell Line
- Chromones/pharmacology
- Enzyme Activation
- Enzyme Inhibitors/pharmacology
- Femur/cytology
- Hematopoietic Stem Cells/cytology/*enzymology
- MAP Kinase Signaling System/*physiology
- Mice
- Mice; Inbred C57BL
- Mitogen-Activated Protein Kinases/metabolism
- Morpholines/pharmacology
- Phosphorylation
- Protein-Serine-Threonine Kinases/metabolism
- Proto-Oncogene Proteins/metabolism
- Proto-Oncogene Proteins c-akt
- Proto-Oncogene Proteins c-kit/*metabolism
- Proto-Oncogene Proteins c-raf/metabolism
- Stem Cell Factor/metabolism
- ras Proteins/metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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