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J. Cell Biol. 164 (7): 1009-1020

Copyright © 2004 by the Rockefeller University Press.


Article

YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3{zeta}

Christian Preisinger1, Benjamin Short1, Veerle De Corte2, Erik Bruyneel3, Alexander Haas1, Robert Kopajtich1, Jan Gettemans2, , and Francis A. Barr1

1 Max-Planck-Institute of Biochemistry, Martinsried, 82152 Germany
2 Department of Biochemistry and Molecular Biology, Faculty of Medicine and Health Sciences, Ghent University/Flanders Interuniversity Institute for Biotechnology (VIB09), B-9000 Ghent, Belgium
3 Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital (1P7), B-9000 Ghent, Belgium

Address correspondence to Francis Barr, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, Martinsried, 82152 Germany. Tel.: 49-89-8578-3135. Fax: 49-89-8578-3102. email: barr{at}biochem.mpg.de

Abstract: The Golgi apparatus has long been suggested to be important for directing secretion to specific sites on the plasma membrane in response to extracellular signaling events. However, the mechanisms by which signaling events are coordinated with Golgi apparatus function remain poorly understood. Here, we identify a scaffolding function for the Golgi matrix protein GM130 that sheds light on how such signaling events may be regulated. We show that the mammalian Ste20 kinases YSK1 and MST4 target to the Golgi apparatus via the Golgi matrix protein GM130. In addition, GM130 binding activates these kinases by promoting autophosphorylation of a conserved threonine within the T-loop. Interference with YSK1 function perturbs perinuclear Golgi organization, cell migration, and invasion into type I collagen. A biochemical screen identifies 14-3-3{zeta} as a specific substrate for YSK1 that localizes to the Golgi apparatus, and potentially links YSK1 signaling at the Golgi apparatus with protein transport events, cell adhesion, and polarity complexes important for cell migration.

Key Words: Ste20 kinases; cell migration; polarity; collagen invasion; scaffold


C. Preisinger, B. Short, and V. De Corte contributed equally to this paper.

The online version of this article contains supplemental material.

Abbreviations used in this paper: MBP, myelin basic protein; MST, mammalian Ste20; siRNA, small interfering RNA; YSK1, yeast Sps1/Ste20-related kinase 1.


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