RRC ID 32585
Author Minami M, Inoue M, Wei S, Takeda K, Matsumoto M, Kishimoto T, Akira S.
Title STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line.
Journal 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.
Volume 93(9)
Pages 3963-6
Published 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
Times Cited 297
DNA material pEF-Flag-mSTAT3 (wild) (RDB02353) pEF-Flag-mSTATY705F (RDB02354).