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Downregulating PKC δ provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression

Oncogene volume 21, pages 1071–1078 (2002)Cite this article

Abstract

3Y1 rat fibroblasts overexpressing the tyrosine kinase c-Src (3Y1c-Src cells) become transformed by downregulation of protein kinase C δ (PKC δ). However, when 3Y1c-Src cells were subjected to serum withdrawal, they underwent apoptosis via a cytochrome c/caspase 9 pathway. In contrast, neither parental nor v-Src-transformed 3Y1 cells underwent apoptosis when subjected to serum withdrawal. If PKC δ was downregulated, the apoptotic phenotypes induced by serum withdrawal in the 3Y1c-Src cells were suppressed. The apparent survival signal generated by PKC δ downregulation was independent of the phosphatidylinositol-3-kinase (PI3K)/Akt survival pathway. Collectively, these data indicate that (1) c-Src overexpression renders cells sensitive to apoptotic stress, and (2) that downregulation of PKC δ provides a novel PI3K/Akt-independent survival signal capable of suppressing apoptotic signals.

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Acknowledgements

We thank Steve Martin for communicating results prior to publication. The dominant negative PKC δ mutant was generously provided by Shigeo Ohno. We thank Dongming Cai and Rebecca James for comments on the manuscript. This investigation was supported by National Institutes of Health grant CA46677. Research Centers in Minority Institutions award RR-03037 from the National Center for Research Resources of the National Institutes of Health, which supports infrastructure and instrumentation in the Biological Sciences Department at Hunter College, is also acknowledged.

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  1. Zhimin Lu

    Present address: The Salk Institute, La Jolla, California, 92037, CA, USA

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  1. Department of Biological Sciences, Hunter College of The City University of New York, New York, 10021, NY, USA

    Minghao Zhong, Zhimin Lu & David A Foster

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Correspondence to David A Foster.

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Zhong, M., Lu, Z. & Foster, D. Downregulating PKC δ provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression. Oncogene 21, 1071–1078 (2002). https://doi.org/10.1038/sj.onc.1205165

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