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Molecular and Cellular Biology, November 2000, p. 8026-8034, Vol. 20, No. 21
Department of Molecular Genetics and the
Comprehensive Cancer Center1 and
Division of Hematology & Oncology,2 Ohio
State University, Columbus, Ohio 43210, and Departments of
Biochemistry and Microbiology and Centre for Molecular and Cellular
Biology, University of Queensland, Brisbane,
Australia3
Received 20 March 2000/Returned for modification 4 May
2000/Accepted 8 August 2000
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.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
ets-2 Is a Target for an Akt (Protein Kinase B)/Jun
N-Terminal Kinase Signaling Pathway in Macrophages of
motheaten-viable Mutant Mice
*
Corresponding author. Mailing address: Department of
Molecular Genetics, Ohio State University, 484 W. 12th Ave., Columbus, OH 43210. Phone: (614) 688-3824. Fax: (614) 688-8727. E-mail: ostrowski.4{at}osu.edu.
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