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Induction of apoptosis by SLK, a Ste20-related kinase

Oncogene volume 18, pages 7566–7575 (1999)Cite this article

Abstract

We have cloned and characterized a novel murine Ste20-related kinase designated SLK. SLK displays high homology to the Ste20-related kinase LOK, and is more distantly related to MST1 and 2, both Ste20-like kinases. In addition, SLK displays high homology to microtubule and nuclear associated protein (M-NAP) and AT1-46, both of unknown function. SLK is ubiquitously expressed as multiple mRNAs in tissues and cell lines and is downregulated by mitogen depletion in differentiating myoblasts. Biochemical characterization showed that SLK overexpression activates c-Jun amino-terminal kinase 1 (JNK1). However, in vitro kinase assays indicated that SLK was not activated in response to various growth factors or stress-inducing agents. Immunofluorescence studies revealed that SLK colocalized to distinct cytosolic domains, preferentially at the periphery of the cells. In addition, prolonged overexpression of SLK in cultured fibroblasts resulted in apoptosis as demonstrated by annexin-V and TUNEL staining. Our results suggest that SLK belongs to a new family of protein kinases, mediating activation of the stress response pathway through a novel signaling cascade.

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Acknowledgements

We thank Catherine Neville and Robert Korneluk for sequencing cDNAs. This work was supported by grants from the Medical Research Council of Canada and the National Institutes of Health to MA Rudnicki. LA Sabourin is supported by a post-doctoral fellowship from the Medical Research Council of Canada. MA Rudnicki is a Research Scientist of the Medicar Research Council of Canada.

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  1. MOBIX, Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada

    Luc A Sabourin & Michael A Rudnicki

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  1. Luc A Sabourin
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Sabourin, L., Rudnicki, M. Induction of apoptosis by SLK, a Ste20-related kinase. Oncogene 18, 7566–7575 (1999). https://doi.org/10.1038/sj.onc.1203119

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