Ets-2 is a target for an Akt (protein kinase B)/Jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice

Smith, James L., Schaffner, Alicia E., Hofmeister, Joseph K., Hartman, Matthew Hartman, Wei, Guo, Forsthoefel, David, Hume, David A. and Ostrowski, Michael C. (2000) Ets-2 is a target for an Akt (protein kinase B)/Jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice. Molecular and Cellular Biology, 20 21: 8026-8034. doi:10.1128/MCB.20.21.8026-8034.2000

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Author Smith, James L.
Schaffner, Alicia E.
Hofmeister, Joseph K.
Hartman, Matthew Hartman
Wei, Guo
Forsthoefel, David
Hume, David A.
Ostrowski, Michael C.
Title Ets-2 is a target for an Akt (protein kinase B)/Jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2000
Sub-type Article (original research)
DOI 10.1128/MCB.20.21.8026-8034.2000
Open Access Status File (Publisher version)
Volume 20
Issue 21
Start page 8026
End page 8034
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2000
Language eng
Abstract 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 mc-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.
Keyword Biochemistry & Molecular Biology
Cell Biology
Tyrosine-phosphatase Shp-1
Hematopoietic-cell Phosphatase
Colony-stimulating Factor
Growth-factor Receptor
Moth-eaten Mice
M-csf Receptor
Protein-kinase
Phosphatidylinositol 3-kinase
Transcription Factor
Bad Phosphorylation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 10 Jun 2008, 12:58:45 EST