@entity7131 ( @entity7131 ) has been implicated in signaling induced by diverse sets of stimuli regulating growth, differentiation, and apoptosis. The present study focused on the fate of @entity7131 isotype proteins during Fas-mediated apoptosis of @entity1 leukemic cell lines. Among the @entity7131 isotypes expressed in different cell types, such as Jurkat, @entity981 , U937, and HL60, all the nPKC isotypes including nPKCdelta, @entity27347 , and nPKCtheta, but not cPKC alpha and betaII and aPKCzeta (n, c, and a represent novel, conventional and atypical, respectively), showed limited proteolytic cleavage during Fas-mediated apoptosis. The limited proteolysis of nPKC isotypes means the disappearance of the intact protein band concomitant with the appearance of two fragments, most likely containing the kinase and regulatory domains, in contrast to the so-called down-regulation known for both cPKC and nPKC isotypes following exposure to stimuli such as @entity864 ( @entity865 ). The time course of Fas-mediated apoptosis in Jurkat cells parallels that of the activation of a 32-kDa @entity462 protease ( @entity522 )-like protease and also closely parallels the proteolytic cleavage of nPKC isotypes. A peptide inhibitor of the @entity522 -like protease, Ac-DEVD- @entity435 , blocked the proteolytic cleavage of nPKC isotypes as well as apoptosis mediated by Fas. Transfection of recombinant protein coding for the catalytic fragment of nPKCdelta to COS1 cells resulted in the apoptotic morphology of cells and nuclei. The effect of @entity865 on apoptosis depends on the cell type. @entity865 significantly suppressed Fas-mediated apoptosis in Jurkat, whereas @entity865 alone caused apoptosis in @entity981 , U937, and HL60, only slight apoptosis in Jurkat. The proteolytic fragmentation of nPKC isotypes again closely correlated with the degree of apoptosis even in apoptosis induced by @entity865 . Separation of @entity865 -treated cells into apoptotic and non-apoptotic differentiating cells revealed that the proteolytic fragmentation of nPKC isotypes occurs only in apoptotic cells and, in adherent differentiating cells, nPKC isotypes as well as cPKC alpha were down-regulated without the generation of nPKC fragments. These results are consistent with the idea that nPKC isotypes meet two different fates, down-regulation and proteolytic cleavage generating kinase and regulatory fragments, and that the proteolytic cleavage of nPKC isotypes is a step in the signaling pathway involved in Fas-mediated and @entity865 -induced apoptosis.

The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, correlates with Fas-mediated and XXXX -induced apoptosis.

@entity1 :: ('9606', 'Species') :: ['human'] @entity27347 :: ('5581', 'Gene') :: ['nPKC epsilon'] @entity981 :: ('MESH:D054198', 'Disease') :: ['HPB-ALL'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity522 :: ('836', 'Gene') :: ['CPP32'] @entity7131 :: ('MESH:D020151', 'Disease') :: ['PKC', 'Protein kinase C'] @entity865 :: ('CHEBI:61432', 'Chemical') :: ['TPA'] @entity864 :: ('MESH:C554292|MESH:D013755', 'Chemical') :: ['12-O-tetradecanoyl-phorbol 13-acetate'] @entity435 :: ('CHEBI:42485', 'Chemical') :: ['CHO']
@entity864 :: (MESH:C554292|MESH:D013755,Chemical) :: ['12-O-tetradecanoyl-phorbol-13-acetate']
