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http://purl.uniprot.org/citations/9738012http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9738012http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9738012http://www.w3.org/2000/01/rdf-schema#comment"Phosphorylation of Bcl2 at serine 70 may result from activation of a classic protein kinase C (PKC) isoform and is required for functional suppression of apoptosis by Bcl2 in murine growth factor-dependent cell lines (Ito, T., Deng, X., Carr, B., and May, W. S. (1997) J. Biol. Chem. 272, 11671-11673). Human pre-B REH cells express high levels of Bcl2 yet remain sensitive to the chemotherapeutic agents etoposide, cytosine arabinoside, and Adriamycin. In contrast, myeloid leukemia-derived HL60 cells express less than half the level of Bcl-2 but are >10-fold more resistant to apoptosis induced by these drugs. The mechanism responsible for this apparent dichotomy appears to involve a deficiency of mitochondrial PKCalpha since 1) HL60 but not REH cells contain highly phosphorylated Bcl2; 2) PKCalpha is the only classical isoform co-localized with Bcl2 in HL60 but not REH mitochondrial membranes; 3) the natural product and potent PKC activator bryostatin-1 induces mitochondrial localization of PKCalpha in association with Bcl2 phosphorylation and increased REH cell resistance to drug-induced apoptosis; 4) PKCalpha can directly phosphorylate wild-type but not phosphorylation-negative and loss of function S70A Bcl2 in vitro; 5) stable, forced expression of exogenous PKCalpha induces mitochondrial localization of PKCalpha, increased Bcl2 phosphorylation and a >10-fold increase in resistance to drug-induced cell death; and () PKCalpha-transduced cells remain highly sensitive to staurosporine, a potent PKC inhibitor. Furthermore, treatment of the PKCalpha transformants with bryostatin-1 leads to even higher levels of mitochondrial PKCalpha, Bcl2 phosphorylation, and REH cell survival following chemotherapy. While these findings strongly support a role for PKCalpha as a functional Bcl2 kinase that can enhance cell resistance to antileukemic chemotherapy, they do not exclude the possibility that another Bcl2 kinase(s) may also exist. Collectively, these findings identify a functional role for PKCalpha in Bcl2 phosphorylation and in resistance to chemotherapy and suggest a novel target for antileukemic strategies."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.org/dc/terms/identifier"doi:10.1074/jbc.273.39.25436"xsd:string
http://purl.uniprot.org/citations/9738012http://purl.org/dc/terms/identifier"doi:10.1074/jbc.273.39.25436"xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"Deng X."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"Deng X."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"May W.S."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"May W.S."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"Ruvolo P.P."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"Ruvolo P.P."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"Carr B.K."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/author"Carr B.K."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/date"1998"xsd:gYear
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/pages"25436-25442"xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/pages"25436-25442"xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/title"A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/title"A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis."xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/volume"273"xsd:string
http://purl.uniprot.org/citations/9738012http://purl.uniprot.org/core/volume"273"xsd:string
http://purl.uniprot.org/citations/9738012http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9738012
http://purl.uniprot.org/citations/9738012http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/9738012
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