2006年8月23日 · Phosphorylation of substrates by Mst results in their activation or inactivation and subsequent downstream effects. Stabilization of Sav by Mst would enhance this process by potentially providing more scaffold ‘sites’ with which to recruit more substrates into the complex, thus strengthening the potential downstream effects.

2017年10月24日 · The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAK SLMAP as a …

2014年11月4日 · MST1/2-SAV1 regulates ciliogenesis through two independent mechanisms: MST1/2 binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the AURKA/HDAC6 cilia-disassembly...

In this study, we show that upstream regulators of the Hippo pathway form functionally antagonizing biomolecular condensates to regulate pathway activity. We further identify the coalescence of these Hippo-regulating condensates as a mechanism for restricting condensate activity without condensate dissolution.

蛋白激酶 Hippo信号通路 由保守的激酶构成，其核心成员是上游的激酶复合物有 MST /SAV/ LATS / MOB 和下游的转录复合物YAP/TAZ- TEADs 组成，YAP/TAZ-TEADs通过控制时间和空间特异性靶基因的表达，调控细胞增殖和凋亡来控制器官大小。 是一条 抑制细胞生长 的信号通路，例如在 骨细胞分化，脂肪细胞分化，肌细胞分化 中都起到一定得调控作用，此外，Hippo信号传导通路不仅在癌症发生和转移、组织再生以及干细胞的功能调控上发挥着重要的作用，同时也受到分子 …

有趣的是, MST1和MST2激酶可促进SAV1与PPARγ结合, 这种结合是由SAV1的WW结构域与PPARγ的PPXY模体介导。 在3T3-L1细胞中, SAV1表达会稳定PPARγ蛋白水平, 而SAV1敲低会导致PPARγ水平降低。SAV1与PPARγ结合可能阻断了PPARγ被泛素化通路元件接近, 并阻止蛋白酶体对PPARγ的降解。 事实上, SAV1可能也与TAZ竞争结合PPARγ, 因为这两个蛋白结合在同一个PPXY模体上。由于MST1/2与SAV1刺激LATS1/2的活性, 它们还可能通过促进TAZ磷酸化使其 …

pression of Mst and hSav led to phosphorylation of hSav and also increased its abundance. In vitro phosphorylation experiments indicate that the phos-phorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst.

2017年2月9日 · Mechanistically, we show that MARK4 binds to and phosphorylates the core components of the Hippo pathway, MST and SAV, and that MARK4, in a kinase‐dependent manner, inhibits the assembly of core the Hippo kinase cassette by disrupting the interaction of MST and SAV with LATS.

2017年10月24日 · 支架蛋白 SAV1 促进了这种激酶级联反应的激活，但分子机制仍然未知。 在这里，我们发现 SAV1 介导的对 PP2A 复合物 STRIPAKSLMAP 的抑制是 MST1/2 激活的关键机制。 SLMAP 与自磷酸化 MST2 接头的结合会招募 STRIPAK，并在激活环处促进 PP2A 介导的 MST2 去磷酸化。 我们的结构和生化研究表明 SAV1 和 MST2 通过其 SARAH 结构域异二聚化。 两个 SAV1–MST2 异源二聚体通过 SAV1 WW 结构域进一步二聚化形成异源四聚体，其中 …

Hpo most closely resembles the pro-apoptotic mammalian sterile20 kinases 1 and 2 (Mst1 and 2), and Salvador (Sav) has a human orthologue hSav (also called hWW45). Here we show that Mst and hSav heterodimerize in an interaction requiring the conserved C-terminal coiled-coil domains of both proteins. hSav was also able to homodimerize, but this ...