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KFC, a Ste20-like kinase with mitogenic potential and capability to activate the SAPK/JNK pathway

Oncogene volume 19, pages 710–718 (2000)Cite this article

Abstract

The Sterile-20 (Ste20) family of serine-threonine kinases has been implicated in the activation of the stress-activated protein kinase pathways. However, the physiological role has remained ambiguous for most of the investigated mammalian Ste20's. Here we report the cloning of a novel Ste20-like kinase, from chicken embryo fibroblast (CEF) cells, which we have named KFC, for Kinase From Chicken. The 898 amino acid full-length KFC protein contains an amino-terminal kinase domain, an adjacent downstream serine-rich region, and a C-terminal tail containing a coiled-coil domain. Here we show that the coiled-coil domain of KFC negatively regulates the intrinsic kinase activity. We have also identified a splice variant of KFC in which there is a 207 nucleotide in-frame deletion. This deletion of 69 amino acids encompasses the serine-rich region. These two isoforms, called KFCL, for full-length, and KFCS for spliced (or short) form, not only differ in structure, but also in biological properties. Stable CEF cells overexpressing KFCL, but not KFCS, have a significant increase in growth rate when compared to parental cells. This mitogenic effect is the first such reported for this family of kinases. Finally, we found that KFC, when activated by truncation of the regulatory C-terminus, has a specific activation of the stress-activated protein kinase (SAPK/JNK) pathway.

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Acknowledgements

We would like to thank Dr Dennis Templeton for pEBG ERK1, SAPK-β, and p38/mHOG constructs, as well as providing the MEKK WT construct used. We also thank Dr Lucy Lee (Michigan State University) for providing us with additional chicken tissues. This work is supported by NIH grants (CA39207, CA46613 and CA57179) to HJ Kung. JT Yustein is supported through the NIH supported Medical Scientist Training Program.

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  1. Deshan Li

    Present address: Copernicus Therapeutics Inc., Cleveland, 44106-3052, Ohio, OH, USA

Authors and Affiliations

  1. Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, 44106-4960, Ohio, OH, USA

    Jason T Yustein, Deshan Li, Dan Robinson & Hsing-Jien Kung

  2. University of California at Davis Cancer Center, Sacramento, 95817, California, CA, USA

    Dan Robinson & Hsing-Jien Kung

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  1. Jason T Yustein
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Yustein, J., Li, D., Robinson, D. et al. KFC, a Ste20-like kinase with mitogenic potential and capability to activate the SAPK/JNK pathway. Oncogene 19, 710–718 (2000). https://doi.org/10.1038/sj.onc.1203342

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