@entity3089 inhibits XXXX signaling pathway. Evidence for direct inhibition of @entity1366 and @entity584 kinases.

@entity3978 @entity470 @entity993 @entity3963 @entity3089 @entity3090 @entity584 @entity876 @entity15308 @entity1977 @entity4012 @entity13525 @entity22564 @entity1366 @entity994
@entity470 ( @entity470 ) activation is absolutely required for cervical cell proliferation. This suggests that @entity470 -inhibitory agents may be of therapeutic value. In the present study, we investigated the effects of @entity3089 ( @entity3090 ), a bioactive green tea @entity3978 , on @entity470 signaling in cervical cells. @entity3090 inhibits epidermal growth factor-dependent activation of @entity470 , and @entity470 -dependent activation of the mitogen-activated protein kinases @entity1366 . @entity3090 also inhibits @entity470 -dependent @entity584 activity. The @entity3090 -dependent reduction in @entity3963 and @entity584 activity is associated with reduced phosphorylation of downstream substrates, including @entity22564 , @entity4012 , and BAD. These changes are associated with increased @entity876 , @entity994 ( @entity994 ), and @entity993 ( @entity13525 ) levels, reduced cyclin E level, and reduced @entity15308 kinase activity. Consistent with these findings, flow cytometry and TUNEL (terminal deoxynucleotidyl-transferase-mediated @entity1977 nick end labeling) staining revealed @entity3090 -dependent G(1) arrest. Moreover, sustained @entity3090 treatment caused apoptotic cell death. In addition to inhibiting @entity470 , cell-free studies demonstrated that @entity3090 directly inhibits @entity1366 and @entity584 , suggesting that @entity3090 acts simultaneously at multiple levels to inhibit EGF-dependent signaling. Importantly, the @entity3090 inhibition is selective, as @entity3090 does not effect the @entity470 -dependent activation of JNK. These results suggest that @entity3090 acts to selectively inhibit multiple EGF-dependent kinases to inhibit cell proliferation.
