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.
Smith
J L
JL
Department of Molecular Genetics and the Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA.
Schaffner
A E
AE
Hofmeister
J K
JK
Hartman
M
M
Wei
G
G
Forsthoefel
D
D
Hume
D A
DA
Ostrowski
M C
MC
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D048057:Mitogen-Activated Protein Kinase 10; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D012097:Repressor Proteins; D051122:Scavenger Receptors, Class B; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D002867:Chromones; D004268:DNA-Binding Proteins; C107465:ERF protein, human; D004791:Enzyme Inhibitors; C494070:Ets2 protein, mouse; D008565:Membrane Proteins; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D012097:Repressor Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D015534:Trans-Activators; D014157:Transcription Factors; D051020:bcl-X Protein; D013912:Threonine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D016173:Macrophage Colony-Stimulating Factor; D048057:Mitogen-Activated Protein Kinase 10; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator