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MEK1-induced Golgi dynamics during cell cycle progression is partly mediated by Polo-like kinase-3

Oncogene volume 23, pages 3822–3829 (2004)Cite this article

Abstract

MEK1, a gene product that regulates cell growth and differentiation, also plays an important role in Golgi breakdown during the cell cycle. We have recently shown that polo-like kinase (Plk3) is Golgi localized and involved in Golgi dynamics during the cell cycle. To study the mode of action of Plk3 in the Golgi fragmentation cascade, we examined functional as well as physical interactions between Plk3 and MEK1/ERKs. In HeLa cells, although a significant amount of Plk3 signals dispersed in a manner similar to those of Golgi during mitosis concentrated Plk3 was detected at spindle poles, which colocalized with phospho-MEKs and phospho-ERKs. Pull-down assays showed that Plk3 physically interacted with MEK1 and ERK2. Nocodazole activated Plk3 and its activation was blocked by MEK-specific inhibitors (PD98059 or U0126). Moreover, transfection of activated MEK1 resulted in an enhanced kinase activity of Plk3; Plk3-induced fragmentation of Golgi stacks was significantly reduced after treatment with MEK inhibitors. Consistently, ectopic expression of activated MEK1, but not kinase-dead MEK1K97R, stimulated Plk3 to induce Golgi breakdown and the stimulation was not observed in cells expressing Plk3K52R. Furthermore, PLK3−/− murine embryonic fibroblast cells exhibited a significantly less fragmentation of the Golgi complex than that in wild-type cells after exposed to nocodazole. Thus, our studies strongly suggest that Plk3 may be a key protein kinase mediating MEK1 function in the Golgi fragmentation pathway during cell division.

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Acknowledgements

We thank Drs Vivek Malhotra and Christine Sutterlin for helpful suggestions and discussions. We also thank Dr John Cogswell at GlaxoSmithKline for pCR259-Plk3 and pCR259-Plk3K52R expression constructs. The work is supported in part by a grant from the National Institutes of Health (RO1-CA74229) to WD and a fellowship award to SX from Philip Morris Research Foundation.

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Authors and Affiliations

  1. Department of Medicine, New York Medical College, Valhalla, 10595, NY, USA

    Suqing Xie, Qi Wang, Qin Ruan, Tongyi Liu & Wei Dai

  2. Institute for Cancer Prevention, Valhalla, 10595, NY, USA

    Meena Jhanwar-Uniyal

  3. Department of Biochemistry, University of Michigan, Ann Arbor, 48109, MI, USA

    Kunliang Guan

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  1. Suqing Xie
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Correspondence to Wei Dai.

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Xie, S., Wang, Q., Ruan, Q. et al. MEK1-induced Golgi dynamics during cell cycle progression is partly mediated by Polo-like kinase-3. Oncogene 23, 3822–3829 (2004). https://doi.org/10.1038/sj.onc.1207479

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