The @entity10242 / @entity8047 / @entity3963 kinase cascade is pivotal in transmitting signals from membrane receptors to transcription factors that control gene expression culminating in the regulation of cell cycle progression. This cascade can prevent cell death through @entity3963 and @entity12328 ( @entity34562 ) activation and phosphorylation of apoptotic and cell cycle regulatory proteins. The @entity10241 / @entity584 kinase cascade also controls apoptosis and can phosphorylate many apoptotic and cell cycle regulatory proteins. These pathways are interwoven as @entity584 can phosphorylate @entity10242 and result in its inactivation, and @entity10242 can be required for the antiapoptotic effects of @entity584 . In this study, the effects of activated @entity10242 ( @entity10242 , A- @entity10242 and @entity817 ) and @entity10241 / @entity584 proteins on abrogation of cytokine @entity734 in FL5.12 hematopoietic cells were examined. Activated @entity10242 , @entity10241 or @entity584 expression, by themselves, did not readily relieve cytokine @entity734 . The presence of activated @entity10242 and @entity10241 / @entity584 increased the isolation of factor-independent cells from 400- to 2500-fold depending upon the particular combination examined. The individual effects of activated @entity10242 and @entity584 on proliferation, apoptosis and autocrine growth factor synthesis were further examined with hormone-inducible constructs (Delta @entity10242 :AR and Delta @entity584 :ER*( @entity17054 (+)). Activation of either @entity10242 or @entity584 hindered cell death; however, both proliferation and maximal synthesis of autocrine cytokines were dependent upon activation of both signaling pathways. The effects of small molecular weight inhibitors on DNA synthesis and cytokine gene expression were also examined. The @entity10241 inhibitor, @entity2306 , inhibited growth and cytokine gene expression. This effect could be synergistically increased by addition of the @entity8047 inhibitor @entity5732 . These cells will be useful in elucidating the interactions between @entity10242 / @entity8047 / @entity3963 and @entity10241 / @entity584 cascades in proliferation, apoptosis, and leukemogenesis, as well as evaluating the efficacy of signal transduction inhibitors that target these cascades.

Effects of the RAF/ @entity8047 / XXXX and @entity10241 / @entity584 signal transduction pathways on the abrogation of cytokine- @entity734 and prevention of apoptosis in hematopoietic cells.

@entity8047 :: ('5609', 'Gene') :: ['MEK'] @entity5732 :: ('MESH:C113580', 'Chemical') :: ['UO126'] @entity3963 :: ('5594', 'Gene') :: ['ERK', 'ERK2'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity2306 :: ('MESH:C085911', 'Chemical') :: ['LY294002'] @entity12328 :: ('57650', 'Gene') :: ['p90'] @entity34562 :: ('6196', 'Gene') :: ['Rsk'] @entity10242 :: ('5894', 'Gene') :: ['Raf', 'Raf-1'] @entity10241 :: ('5295', 'Gene') :: ['PI3K'] @entity17054 :: ('CHEBI:25456', 'Chemical') :: ['Myr'] @entity817 :: ('673', 'Gene') :: ['B-Raf'] @entity734 :: ('MESH:D019966', 'Disease') :: ['dependence']
@entity3963 :: (5594,Gene) :: ['ERK']
