ets-2 Is a Target for an Akt (Protein Kinase B)/Jun N-Terminal Kinase Signaling Pathway in Macrophages of motheaten-viable Mutant Mice
Copyright policy )ets-2 Is a Target for an Akt (Protein Kinase B)/Jun N-Terminal Kinase Signaling Pathway in Macrophages of motheaten-viable Mutant Mice
The transcription factor ets-2 was phosphorylated at residue threonine 72 in a colony-stimulating factor 1 (CSF-1)- and mitogen-activated protein kinase-independent manner in macrophages isolated from motheaten-viable (me-v) mice. The CSF-1 and ets-2 target genes coding for Bcl-x, urokinase plasminogen activator, and scavenger receptor were also expressed at high levels independent of CSF-1 addition to me-v cells. Akt (protein kinase B) was constitutively active in me-v macrophages, and an Akt immunoprecipitate catalyzed phosphorylation of ets-2 at threonine 72. The p54 isoform of c-jun N-terminal kinase-stress-activated kinase (JNK- SAPK) coimmunoprecipitated with Akt from me-v macrophages, and treatment of me-v cells with the specific phosphatidylinositol 3-kinase inhibitor LY294002 decreased cell survival, Akt and JNK kinase activities, ets-2 phosphorylation, and Bcl-x mRNA expression. Therefore, ets-2 is a target for phosphatidylinositol 3-kinase-Akt-JNK action, and the JNK p54 isoform is an ets-2 kinase in macrophages. Constitutive ets-2 activity may contribute to the pathology of me-v mice by increasing expression of genes like the Bcl-x gene that promote macrophage survival.
- University of Queensland Australia
- University of Queensland Australia
- University of Queensland Australia
- University of Edinburgh United Kingdom
- The Ohio State University United States
Threonine, Time Factors, Transcription Factor, Apoptosis, Tyrosine-phosphatase Shp-1, Phosphatidylinositol 3-Kinases, Mice, Mitogen-Activated Protein Kinase 10, Protein Isoforms, Phosphorylation, Receptors, Immunologic, Enzyme Inhibitors, Receptors, Scavenger, Protein-Tyrosine Kinases, Scavenger Receptors, Class B, Protein-Serine-Threonine Kinases, Flow Cytometry, Immunohistochemistry, DNA-Binding Proteins, Proto-Oncogene Proteins c-bcl-2, Colony-stimulating Factor, Mitogen-Activated Protein Kinases, Protein Binding, Signal Transduction, Biochemistry & Molecular Biology, Cell Survival, Morpholines, Blotting, Western, bcl-X Protein, Transfection, Proto-Oncogene Protein c-ets-2, Cell Line, Moth-eaten Mice, Bad Phosphorylation, Proto-Oncogene Proteins, Animals, Receptors, Lipoprotein, Dose-Response Relationship, Drug, Macrophage Colony-Stimulating Factor, Macrophages, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Cell Biology, Blotting, Northern, Precipitin Tests, Urokinase-Type Plasminogen Activator, Protein-kinase, Mice, Mutant Strains, Growth-factor Receptor, Repressor Proteins, Chromones, M-csf Receptor, Trans-Activators, Hematopoietic-cell Phosphatase, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-kinase, Transcription Factors
Threonine, Time Factors, Transcription Factor, Apoptosis, Tyrosine-phosphatase Shp-1, Phosphatidylinositol 3-Kinases, Mice, Mitogen-Activated Protein Kinase 10, Protein Isoforms, Phosphorylation, Receptors, Immunologic, Enzyme Inhibitors, Receptors, Scavenger, Protein-Tyrosine Kinases, Scavenger Receptors, Class B, Protein-Serine-Threonine Kinases, Flow Cytometry, Immunohistochemistry, DNA-Binding Proteins, Proto-Oncogene Proteins c-bcl-2, Colony-stimulating Factor, Mitogen-Activated Protein Kinases, Protein Binding, Signal Transduction, Biochemistry & Molecular Biology, Cell Survival, Morpholines, Blotting, Western, bcl-X Protein, Transfection, Proto-Oncogene Protein c-ets-2, Cell Line, Moth-eaten Mice, Bad Phosphorylation, Proto-Oncogene Proteins, Animals, Receptors, Lipoprotein, Dose-Response Relationship, Drug, Macrophage Colony-Stimulating Factor, Macrophages, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Cell Biology, Blotting, Northern, Precipitin Tests, Urokinase-Type Plasminogen Activator, Protein-kinase, Mice, Mutant Strains, Growth-factor Receptor, Repressor Proteins, Chromones, M-csf Receptor, Trans-Activators, Hematopoietic-cell Phosphatase, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-kinase, Transcription Factors
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