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

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 14-3-3ζ 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.

The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1

“…Although Mst2 is most closely related to Drosophila Hpo and capable of functional complementation (Wu et al, 2003), it seemed possible that other Mst family members could carry out similar functions. We therefore tested two additional Mst kinases for their ability to activate Lats kinases in vitro, notably Mst1, a close homolog of Mst2, and Mst4, a more distant family member implicated in cell migration and polarization (Preisinger et al, 2004). Using the IVT assay described above, we found that both FLAG-Mst2 and Mst1 were able to activate myc-Lats1, whereas Mst4 produced little, if any, activation ( Figure 4b, top row).…”

Germinal center kinases in immune regulation

“…While MST3 is involved in apoptosis, 52 STK25 is involved in cell migration and adhesion. [53][54][55] MST4 was identified as a novel member of the GCK family of STE20 kinases in 2001 and was found to be highly expressed in placenta, thymus and peripheral blood leukocytes. 56,57 The structures of the kinase domains have been determined yet the biological functions of GCK-III in particular remain elusive.…”

“…95 GCK-III kinases may target the Golgi apparatus through binding with GM130 ( Figure 3). 53,96 Despite forming a stable complex, PDCD10 and Striatin may differentially regulate GCK-III. For example, PDCD10 knockdown promotes Golgi localization of MST4 in HeLa cells.…”

Mitogen-activated Protein Kinase Kinase 1-dependent Golgi Unlinking Occurs in G2Phase and Promotes the G2/M Cell Cycle Transition

“…In addition to lateral cross-bridging of Golgi ministacks, GM130/GRASP65 complexes, and possibly golgin45/GRASP55 complexes, also associate with numerous factors on the cytoplasmic face of the Golgi apparatus, including the protein kinases Ysk1, Mst4, and PLK1 (Preisinger et al, 2004;Preisinger et al, 2005). Regulation of these associated factors, rather than Golgi unlinking per se, may be the mechanism facilitating G 2 /M.…”