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 i n a colony-stimulating factor 1 (CSF-1)- and mitogen-activated protein kina se-independent manner in macrophages isolated from motheaten-viable (me-v) mice. The CSF-1 and ets-2 target genes coding for Bcl-x, urokinase plasmino gen activator, and scavenger receptor were also expressed at high levels in dependent of CSF-1 addition to me-v cells. Akt (protein kinase B) was const itutively active in me-v macrophages, and an Akt immunoprecipitate catalyze d phosphorylation of ets-2 at threonine 72. The p54 isoform of c-jun N-term inal kinase-stress-activated kinase (JNK-SAPK) coimmunoprecipitated with Ak t from me-v macrophages, and treatment of mc-v cells with the specific phos phatidylinositol 3-kinase inhibitor LY294002 decreased cell survival, Akt a nd JNK kinase activities, ets-2 phosphorylation, and Bcl-x mRNA expression. Therefore, ets-2 is a target for phosphatidylinositol 3-kinase-Akt-JNK act ion. and the JNK p54 isoform is an ets-2 kinase in macrophages. Constitutiv e 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.