K562 chronic @entity2800 cells are highly resistant to chemotherapeutic drugs, such as @entity1311 , that induce cell death by apoptosis. This resistance is mediated by the chimeric @entity669 kinase oncogene @entity1861 . However, little is known about the mechanism by which @entity1861 protects K562 cells from apoptosis. We recently demonstrated that expression of PKCiota is necessary for the resistance of K562 cells to @entity1311 -induced apoptosis (Murray, N. R., and Fields, A. P. (1997) J. Biol. Chem. 272, 27521-27524). We now demonstrate that treatment of K562 cells with @entity1311 leads to sustained activation of PKCiota. In contrast, @entity1861 -negative HL60 @entity2800 cells, which are sensitive to @entity1311 -induced apoptosis, do not exhibit sustained PKCiota activation in response to @entity1311 . Treatment of K562 cells with @entity42345 , a selective @entity1861 inhibitor, blocks @entity1311 -induced PKCiota activation and sensitizes these cells to @entity1311 -induced apoptosis, indicating that PKCiota is a relevant downstream target of @entity1861 -mediated resistance. Furthermore, expression of constitutively active PKCiota by adenovirus-mediated gene transfer rescues @entity42345 -treated K562 cells from @entity1311 -induced apoptosis. Taken together, these results demonstrate that both @entity1861 and PKCiota activity are necessary for apoptotic resistance in K562 cells. Furthermore, they identify PKCiota as a critical downstream target of @entity1861 that is sufficient to mediate the anti-apoptotic effects of @entity1861 .

Protein kinase Ciota activity is necessary for XXXX -mediated resistance to drug-induced apoptosis.

@entity1861 :: ('25', 'Gene') :: ['Bcr-Abl'] @entity42345 :: ('MESH:C104965', 'Chemical') :: ['AG957', 'tyrphostin AG957'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['taxol'] @entity2800 :: ('MESH:D007951', 'Disease') :: ['myeloid leukemia', 'myelogenous leukemia'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine']
@entity1861 :: (25,Gene) :: ['Bcr-Abl']
