YSK1 is activated by the Golgi matrix protein GM130 and plays a role in cell migration through its substrate 14-3-3zeta.
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 14-3-3zeta 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.
Preisinger
Christian
C
Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, Martinsried, 82152 Germany.
Short
Benjamin
B
De Corte
Veerle
V
Bruyneel
Erik
E
Haas
Alexander
A
Kopajtich
Robert
R
Gettemans
Jan
J
Barr
Francis A
FA
D048948:14-3-3 Proteins; D001324:Autoantigens; D002465:Cell Movement / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013737:Testis / Q000502:physiology / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D000099317:Hippo Kinases
D048948:14-3-3 Proteins; D001324:Autoantigens; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; C097741:Golgin subfamily A member 2; C530660:STK25 protein, human; D000099317:Hippo Kinases