PKC-iota promotes glioblastoma cell survival by phosphorylating and inhibiting BAD through a phosphatidylinositol 3-kinase pathway.

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Desai S, Pillai P, Win-Piazza H, Acevedo-Duncan M

PKC-iota promotes glioblastoma cell survival by phosphorylating and inhibiting BAD through a phosphatidylinositol 3-kinase pathway.

Biochim Biophys Acta. 2011 Jun;1813(6):1190-7. doi: 10.1016/j.bbamcr.2011.03.007. Epub 2011 Mar 17.

PubMed ID
21419810 [ View in PubMed
]
Abstract

The focus of this research was to investigate the role of protein kinase C-iota (PKC-iota) in regulation of Bad, a pro-apoptotic BH3-only molecule of the Bcl-2 family in glioblastoma. Robust expression of PKC-iota is a hallmark of human glioma and benign and malignant meningiomas. The results were obtained from the two human glial tumor derived cell lines, T98G and U87MG. In these cells, PKC-iota co-localized and directly associated with Bad, as shown by immunofluorescence, immunoprecipitation, and Western blotting. Furthermore, in-vitro kinase activity assay showed that PKC-iota directly phosphorylated Bad at phospho specific residues, Ser-112, Ser-136 and Ser-155 which in turn induced inactivation of Bad and disruption of Bad/Bcl-XL dimer. Knockdown of PKC-iota by siRNA exhibited a corresponding reduction in Bad phosphorylation suggesting that PKC-iota may be a Bad kinase. PKC-iota knockdown also induced apoptosis in both the cell lines. Since, PKC-iota is an essential downstream mediator of the PI (3)-kinase, we hypothesize that glioma cell survival is mediated via a PI (3)-kinase/PDK1/PKC-iota/Bad pathway. Treatment with PI (3)-kinase inhibitors Wortmannin and LY294002, as well as PDK1 siRNA, inhibited PKC-iota activity and subsequent phosphorylation of Bad suggesting that PKC-iota regulates the activity of Bad in a PI (3)-kinase dependent manner. Thus, our data suggest that glioma cell survival occurs through a novel PI (3)-kinase/PDK1/PKC-iota/BAD mediated pathway.

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Polypeptides
NameUniProt ID
Protein kinase C iota typeP41743Details