Abstract
The JAK-STAT signal transduction cascade participates in various cellular processes, including immune response, cell replication, differentiation and oncogenesis. Here, we report that this cascade is induced in two human myeloid HL-60 leukemia cell variants by the granulocyte differentiation inducer dimethyl sulfoxide (DMSO) and macrophage differentiation inducer phorbol 12-myristate 13-acetate (PMA). DMSO and PMA also induced the expression and catalytic activity of 2′-5′ oligoadenylate synthetase (2-5A synthetase), a known interferon (IFN) inducible enzyme. The HL-60 cell variants included HL-205, which is susceptible to DMSO- and PMA-induced differentiation, and HL-525, which is susceptible to DMSO- but not to PMA-induced differentiation. Treatment of HL-205 and HL-525 cells with DMSO and HL-205 cells with PMA-induced JAK1 phosphorylation, JAK1/STAT1 association, formation of STAT1-STAT2 heterodimers, and the binding of the active IFN stimulating growth factor 3 (ISGF3) to the IFN-stimulated response element (ISRE) fragment isolated from the 2-5A synthetase promoter. These events were either reduced or absent in the resistant HL-525 cells treated with PMA. Taken together, our data implicate the above signaling cascade in DMSO- and PMA-induced 2-5A synthetase expression and catalytic activity in the HL-60 cell system.
Original language | English |
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Pages (from-to) | 923-931 |
Number of pages | 9 |
Journal | Leukemia Research |
Volume | 29 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2005 |
Bibliographical note
Funding Information:This research was supported by the National Institutes of Health: Grant No. CA80826 to E.H.
Funding
This research was supported by the National Institutes of Health: Grant No. CA80826 to E.H.
Funders | Funder number |
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National Institutes of Health | |
National Cancer Institute | R01CA080826 |
Keywords
- 2′-5′ Oligoadenylate synthetase
- DMSO
- Differentiation
- HL-60
- Interferon stimulated response element
- Interferon-stimulated gene factor complex
- JAK/STAT signaling
- PMA
- Protein kinase C
- STAT1
- STAT2