Sci. STKE, 6 April 2004
CELL MIGRATION Golgi on the Go
It has been hypothesized that the Golgi apparatus participates in cell migration by reorienting in response to extracellular stimuli and by directing secretion toward particular regions of the plasma membrane. The signaling mechanisms that might coordinate such a response, however, have been unclear. Preisinger et al. used immunofluorescence analysis to show that YSK1 (yeast Sps1/Ste20-related kinase 1, a serine-threonine protein kinase) localized to the Golgi in human cell lines. The authors used yeast two-hybrid screens and in vitro binding assays to show that YSK1 bound to the Golgi matrix protein GM130. Depleting cells of GM130 with small interfering RNA (siRNA) abolished YSK1 targeting to the Golgi. Mutational analysis indicated that YSK1 targeting to the Golgi depended on its kinase activity. Moreover, the binding region of GM130 stimulated YSK1 autophosphorylation, thereby activating it. Expression of a dominant-negative YSK1 mutant led to disruption of Golgi localization in HeLa cells, as did YSK1 depletion with siRNA. Dominant-negative YSK1 also abolished HEK293T cell invasion of collagen gels and Golgi reorientation and migration of HS68 cells in response to wounds in the cell monolayer. A biochemical screen indicated that 14-3-3 (which localized to the Golgi) was a substrate for YSK1 and 14-3-3 phosphorylation mutants appropriately opposed or mimicked the effects of dominant-negative YSK1. MST4 (mammalian Ste20 4, a related kinase that also localized to the Golgi and bound and was stimulated by GM130) inhibited HEK293T invasion of collagen gels. Thus YSK1 and MST4, in association with GM130, may play opposing roles in coordinating Golgi function with cell migration.
C. Preisinger, B. Short, V. De Corte, E. Bruyneel, A. Haas, R. Kopajtich, J. Gettemans, F. A. Barr, YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3. J. Cell Biol. 164, 1009-1020 (2004). [Abstract] [Full Text]
Citation: Golgi on the Go. Sci. STKE 2004, tw124 (2004).
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