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MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway

Oncogene volume 20, pages 6559–6569 (2001)Cite this article

Abstract

In this study, we report the cloning and characterization of a novel human Ste20-related kinase that we designated MST4 (accession number AF231012). The 416 amino acid full-length MST4 contains an amino-terminal kinase domain, which is highly homologous to MST3 and SOK, and a unique carboxy-terminal domain. Northern blot analysis indicated that MST4 is highly expressed in placenta, thymus, and peripheral blood leukocytes. Wild-type but not kinase-dead MST4 can phosphorylate myelin basic protein in an in vitro kinase assay. MST4 specifically activates ERK but not JNK or p38 MAPK in transient transfected cells or in stable cell lines. Overexpression of dominant negative MEK1 or treatment with PD98059 abolishes MST4-induced ERK activity, whereas dominant-negative Ras or c-Raf-1 mutants failed to do so, indicating MST4 activates MEK1/ERK via a Ras/Raf-1 independent pathway. HeLa and Phoenix cell lines overexpressing wild-type, but not kinase-dead, MST4 exhibit increased growth rate and form aggressive soft-agar colonies. These phenotypes can be inhibited by PD98059. These results provide the first evidence that MST4 is biologically active in the activation of MEK/ERK pathway and in mediating cell growth and transformation.

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Acknowledgements

We thank Dr M-Z Lai for pFlag-p38 and pHis-ERK plasmid constructs, Dr Y-S Jou for all the hepatoma cell lines and Dr W-C Lin for HR cell. This work was supported by the National Health Research Institutes (to H-M Shih) and NIH grants (to HJ Kung). Unpublished data: J-L Lin, H-I Fang and H-M Shih.

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Authors and Affiliations

  1. Division of Molecular and Genomic Medicine, National Health Research Institutes, 128, Sec2, Yen-Chiu-Yuan RD, Taipei, 11529, Taiwan

    Jei-Liang Lin, Hua-Chien Chen, Hsin-I Fang & Hsiu-Ming Shih

  2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

    Jei-Liang Lin & Hsiu-Ming Shih

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

    Dan Robinson & Hsing-Jien Kung

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  1. Jei-Liang Lin
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Correspondence to Hsiu-Ming Shih.

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Lin, JL., Chen, HC., Fang, HI. et al. MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway. Oncogene 20, 6559–6569 (2001). https://doi.org/10.1038/sj.onc.1204818

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