| RRC ID |
32585
|
| 著者 |
Minami M, Inoue M, Wei S, Takeda K, Matsumoto M, Kishimoto T, Akira S.
|
| タイトル |
STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
Myeloid leukemia M1 cells can be induced for growth arrest and terminal differentiation into macrophages in response to interleukin 6 (IL-6) or leukemia inhibitory factor (LIF). Recently, a large number of cytokines and growth factors have been shown to activate the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. In the case of IL-6 and LIF, which share a signal transducing receptor gp130, STAT3 is specifically tyrosine-phosphorylated and activated by stimulation with each cytokine in various cell types. To know the role of JAK-STAT pathway in M1 differentiation, we have constructed dominant negative forms of STAT3 and established M1 cell lines that constitutively express them. These M1 cells that overexpressed dominant negative forms showed no induction of differentiation-associated markers including Fc gamma receptors, ferritin light chain, and lysozyme after treatment with IL-6. Expression of either c-myb or c-myc was not downregulated. Furthermore, IL-6- and LIF-mediated growth arrest and apoptosis were completely blocked. Thus these findings demonstrate that STAT3 activation is the critical step in a cascade of events that leads to terminal differentiation of M1 cells.
|
| 巻・号 |
93(9)
|
| ページ |
3963-6
|
| 公開日 |
1996-4-30
|
| DOI |
10.1073/pnas.93.9.3963
|
| PMID |
8632998
|
| PMC |
PMC39468
|
| MeSH |
Acute-Phase Proteins / biosynthesis
Acute-Phase Proteins / metabolism
Antigens, CD / physiology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Differentiation / drug effects
Cell Division / drug effects
Cell Line
Cytokine Receptor gp130
DNA-Binding Proteins / biosynthesis
DNA-Binding Proteins / metabolism*
Gene Expression Regulation, Neoplastic / drug effects
Genes, myc
Growth Inhibitors / pharmacology
Humans
Interleukin-6 / pharmacology*
Leukemia Inhibitory Factor
Leukemia, Myeloid, Acute
Lymphokines / pharmacology
Membrane Glycoproteins / physiology*
Mutagenesis, Site-Directed
Oncogenes
Polymerase Chain Reaction
Protein-Tyrosine Kinases / metabolism
Recombinant Proteins / biosynthesis
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology
STAT3 Transcription Factor
Signal Transduction
Trans-Activators / biosynthesis
Trans-Activators / metabolism*
Transfection
Tumor Cells, Cultured
|
| IF |
9.412
|
| 引用数 |
297
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pEF-Flag-mSTAT3 (wild) (RDB02353)
pEF-Flag-mSTATY705F (RDB02354). |
