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MST2 kinase localises at the nucleoli and targets phosphorylation of H2BS14p in an ATM-dependent manner. Ablation of MST2 kinase, or upstream activators, results in defective establishment of nucleolar H2BS14p, perturbed DNA damage repair, sensitisation to rDNA damage and increased cell lethality.
These results suggest Salvador enhances the effects of Hippo kinase activity at multiple points in the Hippo pathway.
Integration analysis of esophageal squamous cell carcinoma (ESCC) identified five hyper-methylated CpG sites in STK3, ZNF418 and ZNF542 that can be used for effective methylation-based testing for ESCC diagnosis.
High MST2 expression is associated with malignant melanoma.
Here, the authors discover SAV1-mediated inhibition of the PP2A complex STRIPAK(SLMAP) as a key mechanism of MST1/2 activation.
Through a comprehensive set of biochemical, biophysical, mutational and structural studies, we quantitatively assess how phosphorylation of MOB1A regulates its interaction with both MST kinases and LATS/NDR family kinases in vitro.
In this study, we investigated the mechanisms behind the recruitment of MST1 and MST2 kinases to MOB1, which facilitate signal transmission in the Hippo pathway by bringing the MST1 and MST2 kinases in close vicinity to their substrates, the LATS family kinases.
Findings indicate that long-term exposure to IM results in dysregulation of stem cell renewal-regulatory Hippo (MST1/2)/YAP signaling, and that inhibition of miR-181a using a microRNA sponge inhibitor resulted in decreased transcription of SOX2 and SALL4.
These findings reveal a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis.
TNFAIP8 regulates Hippo (MST1/2) signaling through its interaction with LATS1.
Data suggest that Hippo (MST1/2 protein kinases) - Yes associated protein 1 (YAP) pathway involved in carcinogenesis of pancreatic cancer and in the inhibition effect of stiehopus japonieus acidic mucopolysaccharide (SJAMP) to the proliferation of pancreatic cancer cell.
H-ras, via an Erk-dependent mechanism, downregulates Mst1/Mst2 activity by inducing the formation of inactive Mst1/Mst2 heterodimers.
Results show that STK3 is targeted by Casp6 and demonstrate that alterations in STK3 protein expression levels and post-translational modifications are detected in a cellular model of HD and caspase-mediated generation of STK3 fragments observed under conditions of stress in cells expressing mhtt.
using an Mst2 mutation that disrupts homotypic dimerization, we showed that the monomeric Mst2-SARAH domain could form a stable complex of 1:1 stoichiometric ratio with WW45 refolded under acidic pH.
The MST1/2-SAV1 complex, a core component of the Hippo pathway, promotes ciliogenesis.
These results suggest that AIF downregulation is a common event in kidney tumor development. AIF loss may lead to decreased STK3 activity, defective apoptosis and malignant transformation
Hippo and Yap regulate cardiomyocyte death and regeneration.
results reveal a novel role of Mst2 in stress-dependent cardiac hypertrophy and remodeling in the adult mouse and likely human heart
Results indicate that changes in phosphorylation orchestrate interactions between kinases and phosphatases in Hippo (MST1/2 protein kinases) signaling, providing a putative mechanism for pathway regulation.
RASSF5 can act as an inhibitor or a potential positive regulator of Mst2, depending on whether it binds to Mst2 before or after activation-loop phosphorylation.
our study reveals a role of Mst1-Mst2 in maintaining the Treg cell pool and functional fitness in vivo, by amplifying IL-2R-STAT5 signal strength and promoting Treg cell migratory ability and access to IL-2.
show that the kinases Mst1 and Mst2 (Mst1/2) sense ROS and maintain cellular redox balance by modulating the stability of antioxidant transcription factor Nrf2.
findings identify Mst1/2 as selective drivers of CD8alpha(+) dendritic cell function by integrating metabolic activity and cytokine signalling, and highlight that the interplay between immune signalling and metabolic reprogramming underlies the unique functions of dendritic cell subsets
It is involved in apoptosis and serine/threonine kinase 3 (STK3) is a recently identified caspase-6 substrate.
Using a standard two-thirds partial hepatectomy (PH) model in young and aged mice, the activity of the core kinases MST1 and LATS1 increased during the early hypertrophic phase and returned to steady state levels in the proliferative phase, coinciding with activation of YAP1 target genes and hepatocyte proliferation.
Studies indicate that Hippo (Hpo; MST1/2 in mammals) signaling pathway plays a central role in the cell fate-specification process.
Mst2 is involved in bone homeostasis, functioning as a reciprocal regulator of osteoclast and osteoblast differentiation through the NF-kappaB pathway
the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity
Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration.
These data indicate that that inhibition of mammalian sterile 20-like kinase 1 rescued cardiac fibrosis and myocardial dysfunction in chronic beta1-adrenergic receptor stimulation-induced cardiomyopathy
Phosphorylation of LC3 by the STK3 and STK4 is essential for autophagy.
These results identify MST2, not MST1, as a critical regulator of caspase-mediated photoreceptor cell death in the detached retina and indicate its potential as a future neuroprotection target.
Mst1/2 regulate placental development by control of trophoblast cell differentiation and labyrinthine vasculature at midgestation and Mst1/2 control labyrinth morphogenesis in trophoblast- and fetal endothelial-dependent manners.
results showed that Mst1/Mst2 are required for proper cardiac lineage cell development and teratoma formation.
these findings indicate that Mst1/2 are important for controlling Treg development and preventing autoimmunity in mice, but also shed new light on our understanding of Mst1 deficiency-mediated human immunodeficiency syndrome.
MST2 maintains postnatal pancreatic acinar differentiation in mice.
Mst1/2 kinases are critical for orchestration of transcription factors involved in surfactant protein homeostasis and prevention of respiratory distress syndrome, and phosphorylate Foxa2, regulating pneumocyte maturation and surfactant protein expression
Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of single positive thymocytes.
Differentiation of 3T3-L1 cells was augmented by MST2 and SAV1 expression and inhibited by knockdown of MST1/2 or SAV1.
Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish.
This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene.
, STE20-like kinase MST2
, mammalian STE20-like protein kinase 2
, serine/threonine kinase 3 (STE20 homolog, yeast)
, serine/threonine kinase 3 (Ste20, yeast homolog)
, serine/threonine-protein kinase 3
, serine/threonine-protein kinase Krs-1
, protein kinase homolog
, serine/threonine kinase 3 (STE20 homolog)