The Ste20-like Kinase SLK Is Required for Cell Cycle Progression through G2

Katia Cailliau,Paul G. O'Reilly,Simona Wagner,Luc A. Sabourin,Douglas J. Franks,Colette Dissous,Edith Browaeys

doi:10.1074/jbc.m510763200

Abstract

We have previously shown that the Ste20-like kinase SLK is a microtubule-associated protein that can regulate actin reorganization during cell adhesion and spreading (Wagner, S., Flood, T. A., O'Reilly, P., Hume, K., and Sabourin, L. A. (2002) J. Biol. Chem. 277, 37685-37692). Because of its association with the microtubule network, we investigated whether SLK plays a role in cell cycle progression, a process that requires microtubule dynamics during mitosis. Consistent with microtubule association in exponentially growing cells, our results showed that SLK co-localizes with the mitotic spindle in cells undergoing mitosis. Expression of a kinase-inactive mutant or SLK small interfering RNAs inhibited cell proliferation and resulted in an accumulation of quiescent cells stimulated to re-enter the cell cycle in the G2 phase. Cultures expressing the mutant SLK displayed a normal pattern of cyclin D, E, and B expression but failed to down-regulate cyclin A levels, suggesting that they cannot proceed through M phase. In addition, these cultures displayed low levels of both phospho-H3 and active p34/cdc2 kinase. Overexpression of active SLK resulted in ectopic spindle assembly and the induction of cell cycle re-entry of Xenopus oocytes, suggesting that SLK is required for progression through G2 upstream of H1 kinase activation.

Highlights

Cell cycle progression is monitored through kinase-mediated signal transduction and the binding of various cyclin proteins to their respective cyclin-dependent kinases (Cdks [2, 3])
D, cultures infected with an adenovirus bearing a kinase-inactive version of Ste20-like kinase (SLK) (K⌬C) were collected over time, and viable cells were counted by trypan blue exclusion
Cell cycle progression is regulated by complex signaling networks involving post-translational modification, gene expression, and cytoskeletal reorganization

Summary

Introduction

Cell cycle progression is monitored through kinase-mediated signal transduction and the binding of various cyclin proteins to their respective cyclin-dependent kinases (Cdks [2, 3]). The observation that SLK is associated with the microtubule network [1] and that it was shown to phosphorylate and activate Plk [33] prompted us to investigate the role of SLK in cell cycle progression.

Results

Conclusion