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

被引:220
作者
Preisinger, C
Short, B
De Corte, V
Bruyneel, E
Haas, A
Kopajtich, R
Gettemans, J
Barr, FA
机构
[1] Max Planck Inst Biochem, D-82152 Martinsried, Germany
[2] State Univ Ghent VIB, Fac Med & Hlth Sci, Dept Biochem & Mol Biol, B-9000 Ghent, Belgium
[3] Ghent Univ Hosp, Dept Radiotherapy & Nucl Med, Expt Cancerol Lab, B-9000 Ghent, Belgium
关键词
Ste20; kinases; cell migration; polarity; collagen invasion; scaffold;
D O I
10.1083/jcb.200310061
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 1 collagen. A biochemical screen identifies 14-3-3zeta 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.
引用
收藏
页码:1009 / 1020
页数:12
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