Affinage

MST1

Hepatocyte growth factor-like protein · UniProt P26927

Audit flag: wrong gene
Length
711 aa
Mass
80.3 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MST1 (STK4) is a Ste20-family serine/threonine kinase that serves as a central integrator of growth-suppressive, apoptotic, and immune-regulatory signaling, most prominently as the apical kinase of the Hippo tumor-suppressor cascade (PMID:19878874, PMID:20080598). The kinase homodimerizes through its extreme C-terminal SARAH domain and is held in check by a central inhibitory region; full activation requires intermolecular autophosphorylation of the activation loop at Thr183/Thr187, which is potentiated by dimerization (PMID:8702870, PMID:12223493). A second, irreversible activation route is caspase-3 cleavage, which excises the C-terminal regulatory domain bearing nuclear export signals, freeing the kinase domain to enter the nucleus, phosphorylate histones, and drive chromatin condensation and apoptosis (PMID:9545236, PMID:11517310). In the Hippo pathway, MST1 phosphorylates MOB1/MOBKL1, which licenses LATS-mediated inactivating phosphorylation of YAP, restraining proliferation and tumorigenesis in liver and other tissues (PMID:18328708, PMID:19878874). Beyond Hippo, MST1 phosphorylates a broad substrate set to enforce apoptosis and cellular homeostasis, including FOXO1/3 (disrupting 14-3-3 binding to drive nuclear import and death) (PMID:19221179), Bcl-xL at a mitochondrial complex (PMID:24813943), PDX1 (triggering its degradation in beta cells) (PMID:24633305), Aurora B (ensuring accurate kinetochore-microtubule attachment) (PMID:20171103), AURKA (promoting ciliogenesis) (PMID:25367221), and the antiviral factor IRF3 and the LUBAC component HOIP (both attenuating innate-immune transcriptional output) (PMID:27125670, PMID:30901564). In lymphocytes and myeloid cells MST1 governs adhesion, trafficking, and effector function largely through MOB1-DOCK8-Rac/RhoA signaling and cytoskeletal substrates such as L-plastin (PMID:19073936, PMID:19339990, PMID:22412158, PMID:27465533, PMID:30413360). MST1 activity is tuned by an extensive regulatory network: it is inhibited by Akt (Thr120), mTORC2 (Ser438), and FGFR4 (Tyr433), activated by c-Abl (Tyr433) and the phosphatase PHLPP (removing inhibitory Thr387), and its protein level is set by opposing ubiquitin machineries stabilized by USP46 and degraded via SIRT7/TRAF6 (PMID:20513427, PMID:21715626, PMID:25843706, PMID:19940129, PMID:30903103, PMID:38288904, PMID:34029571). Scaffold proteins of the RASSF/Nore1 family and SAV1 bind MST1 via SARAH domains and bias its substrate selectivity (PMID:16757333, PMID:28327630).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Established the autoregulatory architecture of MST1 — how a constitutively folded kinase keeps itself off — by mapping a C-terminal dimerization module and a separable central inhibitory domain.

    Evidence Deletion mutagenesis with Co-IP, yeast two-hybrid, cross-linking, and size exclusion chromatography

    PMID:8702870

    Open questions at the time
    • Did not identify the physiological trigger that relieves inhibition
    • No structure of the autoinhibited dimer
  2. 1998 High

    Defined caspase-3 cleavage as an apoptotic activation switch, showing MST1 is both an effector and amplifier of cell death through a caspase feedback loop and stress-kinase activation.

    Evidence Caspase inhibitor pharmacology, in vivo cleavage assays, and kinase-dead/truncation overexpression during Fas and staurosporine apoptosis

    PMID:9545236

    Open questions at the time
    • Did not resolve whether cleavage is required versus sufficient for physiological apoptosis
    • Downstream substrates of nuclear MST1 not yet identified
  3. 2001 High

    Explained how cleavage couples to function spatially: removal of the C-terminal NES-bearing fragment relocalizes the kinase to the nucleus, linking cleavage to chromatin condensation.

    Evidence NES mutagenesis, leptomycin B export inhibition, and subcellular fractionation in apoptotic cells (PNAS); JNK-dependence and CAD-mediated DNA fragmentation epistasis (Genes Cells)

    PMID:11442632 PMID:11517310

    Open questions at the time
    • Nuclear substrates driving condensation not defined
    • Relative contribution of caspase-dependent versus JNK arms left unquantified
  4. 2002 High

    Mapped the activating phosphorylation code (Thr183/Thr187 by dimerization-enhanced intermolecular autophosphorylation) and identified the first direct binding partner augmenting apoptosis.

    Evidence Site-directed mutagenesis with in vitro kinase and detachment/apoptosis assays (JBC); DAP4 Co-IP and p53-dependence (JBC)

    PMID:12223493 PMID:12384512

    Open questions at the time
    • Upstream kinase versus pure autophosphorylation contributions unresolved
    • DAP4 link to p53 functional consequence inferred, not reconstituted
  5. 2006 Medium

    Reconstituted spontaneous dimer autoactivation in vitro and showed RASSF/Nore1 scaffolds act through the SARAH domain to control activation, establishing membrane recruitment as an activating context.

    Evidence In vitro kinase reconstitution, SARAH binding assays, and membrane/Ras recruitment experiments

    PMID:16757333

    Open questions at the time
    • Methods-paper format limits independent functional follow-up
    • Direction of RASSF effect (inhibit vs. recruit-activate) context-dependent and unresolved
  6. 2007 Medium

    Positioned MST1 in reciprocal antagonism with Akt, identifying it as a lipid-raft Akt1 interactor and inhibitor relevant to survival signaling.

    Evidence Co-IP from lipid raft fractions, endogenous kinase activity assays, and zebrafish rescue of membrane-Akt1 lethality

    PMID:17932490

    Open questions at the time
    • Mechanism of Akt inhibition (catalytic vs. sequestration) not defined
    • Reciprocal Akt-on-MST1 regulation addressed only later
  7. 2008 High

    Identified MOB1/MOBKL1 as the direct substrate connecting MST1 to LATS activation, anchoring MST1 as an apical Hippo kinase controlling cell-cycle progression.

    Evidence In vitro kinase assays, MST-dependent cellular phosphorylation, and non-phosphorylatable MOB knock-in with cell-cycle analysis

    PMID:18328708

    Open questions at the time
    • Did not establish in vivo organ-size relevance (addressed in genetic models)
    • Mitotic activation trigger upstream of MST1 unclear
  8. 2009 High

    Genetic loss-of-function across multiple systems revealed MST1's physiological roles: T-cell proliferation/adhesion control, neuronal FOXO1-dependent death, and bona fide liver tumor suppression via YAP inactivation.

    Evidence MST1-knockout T cells with substrate phosphorylation and adhesion assays (PNAS, EMBO J); FOXO1 Ser212 phosphorylation and 14-3-3 dissociation in neurons (JBC); conditional liver Mst1/2 KO with YAP Ser127 and HCC rescue (Cancer Cell); Akt phosphorylation of MST1 Thr120 (JBC)

    PMID:19073936 PMID:19221179 PMID:19339990 PMID:19878874 PMID:19940129

    Open questions at the time
    • Liver YAP regulation attributed to a LATS-distinct intermediary kinase not identified
    • Tissue-specific substrate selection mechanisms unresolved
  9. 2010 High

    Solidified MST1/2 redundancy in organ-size/tumor control and expanded the substrate repertoire to mitotic fidelity (Aurora B) and apoptotic transcription (Sirt1-p53), while defining the PHLPP/Akt/Thr387 activity rheostat.

    Evidence Mst1/2 double-KO mice with YAP and TNFα-apoptosis readouts (PNAS); MST1 RNAi with in vitro Aurora B phosphorylation and checkpoint rescue (Curr Biol); PHLPP phosphatase and Akt Thr387 kinase assays (Mol Cell); MST1-Sirt1-p53 kinase and acetylation assays (JBC)

    PMID:20080598 PMID:20171103 PMID:20513427 PMID:21212262

    Open questions at the time
    • Integration of mitotic versus Hippo roles in vivo not dissected
    • Sirt1-p53 axis confidence medium and not validated in knockout
  10. 2011 High

    Defined tyrosine-kinase inputs and ubiquitin-dependent stability control, showing c-Abl phosphorylation at Tyr433 stabilizes and activates MST1 to drive FOXO3-dependent neuronal death under oxidative stress.

    Evidence In vitro c-Abl kinase assay, CHIP ubiquitination assay, and MST1-FOXO3 Co-IP in primary neurons

    PMID:21715626

    Open questions at the time
    • Interplay between Tyr433 and the later-defined FGFR4 phosphorylation at the same residue unaddressed
    • CHIP versus other E3 ligase contributions not delineated
  11. 2012 High

    Mechanistically linked MST1 to immune-cell motility by showing phospho-MOB1 recruits the Rac GEF DOCK8, activating Rac1/RhoA to drive thymic egress and migration.

    Evidence Mst1/2 double-KO thymocytes with GTP-charging assays and phospho-Mob1/DOCK8 Co-IP

    PMID:22412158

    Open questions at the time
    • How a Hippo-core substrate (MOB1) is rewired to cytoskeletal output is not structurally explained
  12. 2014 High

    Extended direct substrate phosphorylation to metabolic and cardiac contexts — PDX1 degradation in beta cells, Bcl-xL Ser14 at mitochondria — and identified the basal-body/AURKA ciliogenesis function.

    Evidence In vitro kinase assays with site mapping plus KO/transgenic mice (Nat Med, PDX1); mitochondrial K-Ras/RASSF1A/Mst1 complex and Bcl-xL assays (Mol Cell); AURKA phosphorylation and ciliogenesis in cells/zebrafish (Nat Commun)

    PMID:24633305 PMID:24813943 PMID:25367221

    Open questions at the time
    • Determinants of substrate choice across these contexts not defined
    • Relationship of ciliary AURKA role to mitotic AURKA role unaddressed
  13. 2015 High

    Defined mTORC2 as a direct negative regulator phosphorylating Ser438 to block dimerization, and assigned MST1/2 a role in innate immunity by directing mitochondrial recruitment to phagosomes.

    Evidence In vitro mTORC2 kinase assay with S438 mutagenesis and cardiac Rictor KO (Cell Rep); Mst1/2-KO macrophages with Rac activation, TRAF6-ECSIT Co-IP, and ROS/bactericidal assays (Nat Immunol)

    PMID:25843706 PMID:26414765

    Open questions at the time
    • How a SARAH-domain phosphorylation mechanistically disrupts dimer interface not structurally resolved
  14. 2016 High

    Established MST1 as a brake on innate antiviral signaling (IRF3) and on NF-κB-promoting Th17 responses, and revealed scaffold (DLG5)- and heterodimerization-based mechanisms that suppress MST1 kinase output; also delivered a structurally validated chemical probe (XMU-MP-1) and additional substrates (L-plastin).

    Evidence MST1-IRF3 kinase/dimerization assays and KO viral challenge (Genes Dev); DLG5 AP-MS with genetic rescue (Genes Dev); Mst1/Mst2 heterodimer Co-IP and kinase comparison (Curr Biol); XMU-MP-1 co-crystal and regeneration models (Sci Transl Med); L-plastin Thr89 kinase assay (J Immunol); DC-specific MST1 KO p38-IL6-STAT3 axis (Nat Commun); hepatic Sirt1 stabilization in KO mice (BBRC)

    PMID:26903296 PMID:27125670 PMID:27238285 PMID:27465533 PMID:27535619 PMID:28087714 PMID:28145433

    Open questions at the time
    • MST2-specific divergence from MST1 (e.g., IRF3) mechanistically unexplained
    • Whether scaffold-based inhibition operates in all tissues unresolved
  15. 2017 Medium

    Showed RASSF SARAH heterodimerization biases MST1 substrate selectivity — promoting H2B but suppressing FoxO phosphorylation — providing a mechanism for context-specific output, and added the angiogenic ROS-MST1-FOXO1 endothelial cascade.

    Evidence SPR domain mapping with in vitro multi-substrate kinase assays (Sci Rep); endothelial-specific MST1/FOXO1 KO with sprouting angiogenesis models (Nat Commun)

    PMID:28327630 PMID:30783090

    Open questions at the time
    • Structural basis for scaffold-directed substrate switching not determined
    • RASSF effects assayed only in vitro for substrate selectivity
  16. 2018 High

    Placed MST1 inside the TNF receptor signaling complex as a HOIP/LUBAC-phosphorylating brake on NF-κB, defining a direct non-Hippo immune-regulatory mechanism.

    Evidence MST1-TNF-RSC Co-IP, in vitro HOIP kinase assay, LUBAC ubiquitination assay, and MST1-KO NF-κB readouts; Treg DOCK8-LRCHs proteomics and Rac/STAT5 assays (Immunity)

    PMID:30413360 PMID:30901564

    Open questions at the time
    • How catalytic activity is engaged within the TNF-RSC not detailed
    • Coordination of MST1 immune-regulatory roles with its Hippo role unresolved
  17. 2019 High

    Expanded the direct-substrate map into neuronal (UNC5B, p53), reproductive (Nur77), and identified additional negative regulation by FGFR4 at Tyr433, plus Hippo-independent ROS-pyroptosis tumor suppression.

    Evidence In vitro kinase assays with site mapping and KO/rescue for UNC5B Thr428 (PNAS) and Nur77 Thr366 (EBioMedicine); FGFR4 MS-confirmed Tyr433 phosphorylation and mutagenesis (Cell Death Differ); MST1 overexpression caspase-1 pyroptosis with NAC rescue (Mol Cancer Res)

    PMID:30796177 PMID:30903103 PMID:32929029 PMID:36623453

    Open questions at the time
    • FGFR4 and c-Abl both target Tyr433 with opposite outcomes — reconciliation unresolved
    • Pyroptosis mechanism medium-confidence, not reconstituted in vitro
  18. 2021 Medium

    Resolved opposing ubiquitin-dependent control of MST1 abundance, with USP46 stabilizing MST1 to enforce YAP suppression and TRAF6 mediating LPS-induced MST1 ubiquitination in a reciprocal NF-κB feedback loop.

    Evidence USP46-MST1 Co-IP and ubiquitination/stability assays with HCC models (Exp Cell Res); myeloid-specific MST1 KO with TRAF6 autoubiquitination assays and septic-shock model (CMLS)

    PMID:32975614 PMID:34029571

    Open questions at the time
    • E3 ligase(s) opposed by USP46 not identified
    • Whether USP46 and TRAF6 act on the same MST1 pool unaddressed
  19. 2022 Medium

    Added cardiovascular (Cx43 Ser255 hemichannel closure) and neurodegenerative (p53-dependent AD-like deficits) functions, broadening MST1's role in endothelial activation and cognition.

    Evidence MS substrate identification with hemichannel dye-uptake assay and EC-specific Mst1-KO atherosclerosis model (Circ Res); MST1-p53 Co-IP and p53-KO rescue in 5xFAD mice (Prog Neurobiol)

    PMID:35525373 PMID:36164986

    Open questions at the time
    • p53 phosphorylation site not formally mapped
    • Mechanistic overlap with earlier MST1-Sirt1-p53 axis not integrated
  20. 2024 High

    Defined transcriptional plus post-translational suppression of MST1 by SIRT7, linking deacetylase activity to MST1 promoter repression and acetylation-primed degradation that releases YAP in liver cancer.

    Evidence ChIP for SIRT7/H3K18ac on the MST1 promoter, SIRT7-MST1 Co-IP, MS deacetylation site mapping, ubiquitination assay, and xenograft model

    PMID:38288904

    Open questions at the time
    • The acetylation-dependent E3 ligase not identified
    • Relationship between SIRT7 and USP46/TRAF6 control of MST1 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how MST1 selects among its many divergent substrates and reconciles opposing inputs converging on shared residues (e.g., c-Abl versus FGFR4 at Tyr433), and how scaffold context dictates whether MST1 drives Hippo, apoptotic, or immune-regulatory outputs.
  • No structural model of substrate-selecting MST1 complexes
  • No unified framework integrating tissue-specific scaffolds with substrate choice
  • Convergence of opposing tyrosine-kinase inputs at Tyr433 mechanistically unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 13 GO:0016740 transferase activity 4 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 2
Partners
AKT1AURKBDOCK8HOIPMOB1RASSF1SAV1USP46
Complex memberships
K-Ras/RASSF1A/MST1 mitochondrial complexMST1/2-SAV1 complexTNF receptor signaling complex (TNF-RSC)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 MST1 homodimerizes via its extreme C-terminal 57 amino acids, and contains an inhibitory domain within a central 63-amino acid region whose removal increases kinase activity ~9-fold. Loss of dimerization alone does not affect kinase activity, but a molecule lacking both the dimerization and inhibitory domains is less active than one lacking only the inhibitory domain. MST1 also associates with a high molecular weight complex in cells. C-terminal and internal deletion analysis, co-immunoprecipitation, yeast two-hybrid, in vitro cross-linking, size exclusion chromatography The Journal of biological chemistry High 8702870
1998 MST1 is specifically cleaved by caspase-3-like activity (blocked by ZVAD-fmk, DEVD-CHO, and CrmA) during Fas/CD95- or staurosporine-induced apoptosis, removing the C-terminal regulatory domain and activating MST1. Overexpression of wild-type or truncated MST1 induces apoptotic morphology; kinase-dead MST1 does not. Activated MST1 activates MKK6, p38 MAPK, MKK7, and SAPK in co-transfection assays. MST1 can also activate caspases that in turn cleave it, forming a positive feedback loop. Caspase inhibitor experiments, in vivo cleavage assays, overexpression of wild-type and kinase-dead mutants, co-transfection kinase activation assays The EMBO journal High 9545236
2001 Caspase-mediated cleavage of MST1 releases the C-terminal domain containing two functional nuclear export signals (NESs), causing nuclear translocation of the N-terminal kinase domain. Full-length MST1 is cytoplasmic; truncation of the C-terminal domain, NES point mutation, or leptomycin B treatment causes nuclear localization. Nuclear MST1 is more efficient at inducing chromatin condensation; inhibiting cleavage-site mutation reduces chromatin condensation ability. NES mutation, leptomycin B treatment, subcellular fractionation/localization, staurosporine-induced apoptosis assays, kinase-negative mutant expression Proceedings of the National Academy of Sciences of the United States of America High 11517310
2001 MST1 promotes apoptosis through JNK activation: dominant-negative JNK inhibits MST1-induced morphological changes and caspase-3 activation. MST1 induces CAD-mediated DNA fragmentation via caspase-dependent pathway and induces chromatin condensation and membrane blebbing through a caspase-independent JNK pathway. p38 MAPK is not required for MST1-induced apoptosis. Dominant-negative JNK co-expression, p38 inhibitor (SB203580), caspase inhibitors, ICAD expression, morphological assays Genes to cells : devoted to molecular & cellular mechanisms Medium 11442632
2002 MST1 activation requires phosphorylation at Thr183 (primary site) and Thr187 in subdomain VIII, catalyzed by intermolecular autophosphorylation enhanced by homodimerization. Active MST1 also autophosphorylates at Thr177 and Thr387. Active MST1 activates JNK, caspase-3, and caspase-9. Kinase activity (not caspase cleavage) is required for apoptotic cell detachment. An S327E phosphomimetic mutant confers caspase resistance. Site-directed mutagenesis of phosphorylation sites, in vitro kinase assays, cell detachment and apoptosis assays with phospho-mimetic and phospho-dead mutants The Journal of biological chemistry High 12223493
2002 Death-associated protein 4 (DAP4) binds MST1 through its carboxyl-terminal segment and co-localizes with MST1 in cells. DAP4 does not alter MST1 kinase activity but augments MST1-induced apoptosis in a dose-dependent manner when co-expressed with sub-maximal MST1. MST1-induced apoptosis is suppressed by dominant-negative p53, and DAP4 binds p53, potentially enabling MST1 colocalization with p53. Co-immunoprecipitation, overexpression co-transfection apoptosis assays, dominant-negative p53, in vitro kinase assay The Journal of biological chemistry Medium 12384512
2006 RASSF1/Nore1 polypeptides bind MST1 and MST2 through SARAH domain interactions. Recombinant MST1/2, spontaneous dimers, autoactivate in vitro through intradimer transphosphorylation of the activation loop; Nore1/RASSF1 polypeptides inhibit this autoactivation. Membrane-recruited MST1 is strongly activated in vivo; MST1 bound to RasG12V through Nore1A is activated. In vitro kinase reconstitution, SARAH domain binding assays, membrane recruitment experiments, co-immunoprecipitation of endogenous complexes Methods in enzymology Medium 16757333
2007 MST1 is a physiological interaction partner of Akt1, identified in lipid raft-enriched fractions from prostate cancer cells. Endogenous MST1 (and MST2) inhibit endogenous Akt1 activity. Both full-length MST1 and its two caspase cleavage products complex with and inhibit Akt1. MST1 cRNAs revert an early lethal phenotype in zebrafish induced by membrane-targeted Akt1. Co-immunoprecipitation from lipid raft fractions, endogenous kinase activity assays, zebrafish rescue experiments The EMBO journal Medium 17932490
2008 MST1 and MST2 are activated during mitosis (especially in nocodazole-arrested cells). MST1/2 phosphorylate MOBKL1A and MOBKL1B (Drosophila MATS homologs) in vitro and in cells in an MST1/2-dependent manner during mitosis and in response to okadaic acid or H2O2. MST1/2-catalyzed MOB phosphorylation promotes MOB binding to LATS1 and enables H2O2-stimulated LATS1 activation loop phosphorylation. Non-phosphorylatable MOB mutant replacement accelerates cell proliferation by speeding G1/S and mitotic exit. In vitro kinase assays, cell-based phosphorylation with MST1/2 knockdown/overexpression, replacement of endogenous MOB with non-phosphorylatable mutant, cell cycle analysis Current biology : CB High 18328708
2008 The Nore1B/RAPL-MST1 complex restrains antigen receptor-induced proliferation of naive T cells. MST1-null naive T cells show markedly greater TCR-stimulated proliferation; among known MST1 substrates, only MOBKL1A/B phosphorylation is entirely lost in TCR-stimulated, MST1-deficient T cells. MST1-null T cells exhibit defective LFA-1 clustering. Mst1-null mice have reduced Nore1B/RAPL in lymphoid cells. MST1 knockout mice, in vitro proliferation assays, substrate phosphorylation analysis, LFA-1 clustering microscopy Proceedings of the National Academy of Sciences of the United States of America High 19073936
2009 MST1 phosphorylates FOXO1 at Ser212 (corresponding to Ser207 in FOXO3), disrupting FOXO1 association with 14-3-3 proteins and promoting FOXO1 nuclear translocation in cerebellar granule neurons deprived of neuronal activity. MST1 is required for neuronal death upon growth factor/activity withdrawal, and MST1 promotes cell death in a FOXO1-dependent manner. The scaffold protein Nore1 is also required for survival factor deprivation-induced neuronal death. Phosphorylation assays, 14-3-3 co-immunoprecipitation, nuclear translocation imaging, MST1 loss-of-function in primary neurons, FOXO1-dependent rescue experiments The Journal of biological chemistry High 19221179
2009 Mst1 and Mst2 are cleaved and constitutively activated in mouse liver. Combined Mst1/2 deficiency leads to loss of inhibitory Ser127 phosphorylation of YAP1, liver overgrowth, and hepatocellular carcinoma. Re-expression of Mst1 in HCC cell lines promotes YAP1 Ser127 phosphorylation/inactivation and abolishes tumorigenicity. Mst1/2 inactivates YAP1 in liver through an intermediary kinase distinct from Lats1/2. Conditional liver-specific Mst1/2 knockout mice, YAP1 phosphorylation western blot, HCC cell line re-expression with tumorigenicity assays, epistasis analysis Cancer cell High 19878874
2009 Mst1 is required for lymphocyte trafficking in vivo. Mst1-/- lymphocytes show impaired firm adhesion to high endothelial venules and reduced stopping time on endothelium under physiological shear, defective stabilization of α4 integrin-mediated adhesion, and impaired motility within lymph nodes. L-selectin-dependent rolling/tethering was not affected. Mst1 knockout mice, in vitro adhesion cascade assays under shear flow, intravital imaging within lymph nodes The EMBO journal High 19339990
2010 Mst1 and Mst2 act redundantly to control organ size and suppress tumorigenesis; combined deletion (Mst1-/-; Mst2-/-) causes early embryonic lethality and is required to control YAP phosphorylation and activity in vivo. TNFα-induced apoptosis is blocked in Mst1/Mst2 double-mutant cells both in vivo and in vitro. Mst1/Mst2 double-knockout mice, YAP phosphorylation assays, TNFα-induced apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 20080598
2010 MST1 promotes accurate kinetochore-microtubule attachment by phosphorylating Aurora B directly (in vitro), inhibiting its kinase activity. MST1 depletion increases Aurora B activity and causes unaligned mitotic chromosomes with Mad2/BubR1-dependent spindle checkpoint activation. MST1 and NDR1 (downstream kinase of MST1) associate with Aurora B; NDR1 depletion phenocopies MST1 depletion; Aurora B depletion rescues kinetochore-microtubule attachment defects in MST1/NDR1-depleted cells. MST1/NDR1 RNAi, in vitro kinase assay (MST1 phosphorylation of Aurora B), co-immunoprecipitation, live-cell microscopy, spindle checkpoint assay Current biology : CB High 20171103
2010 PHLPP phosphatases bind MST1 both in vivo and in vitro, dephosphorylate MST1 at inhibitory Thr387, activating MST1 and its downstream effectors p38 and JNK to induce apoptosis. Akt phosphorylates Thr387 to inhibit MST1. PHLPP, Akt, and MST1 form an autoinhibitory triangle controlling apoptosis/proliferation balance. Co-immunoprecipitation, in vitro phosphatase and kinase assays, mutant MST1 T387 analysis, p38/JNK activation assays Molecular cell High 20513427
2011 c-Abl tyrosine kinase phosphorylates MST1 at Tyr433, triggering MST1 stabilization and activation. Inhibition of c-Abl promotes MST1 degradation via CHIP-mediated ubiquitination. Oxidative stress induces c-Abl-dependent tyrosine phosphorylation of MST1 and increases the MST1-FOXO3 interaction, activating the MST1-FOXO signaling pathway leading to neuronal cell death. In vitro kinase assay (c-Abl phosphorylation of MST1), c-Abl inhibitor/RNAi, CHIP ubiquitination assays, co-immunoprecipitation (MST1-FOXO3), primary neuron and hippocampal neuron assays The Journal of neuroscience : the official journal of the Society for Neuroscience High 21715626
2011 MST1 promotes apoptosis in a p53-dependent manner by phosphorylating Sirt1, inhibiting its deacetylase activity and its interaction with p53, thereby increasing p53 acetylation and transactivation. This defines an MST1-Sirt1-p53 signaling axis in DNA damage-induced apoptosis. In vitro kinase assay (MST1 phosphorylation of Sirt1), co-immunoprecipitation (Sirt1-p53), Sirt1 activity assay, p53 acetylation/transactivation assays The Journal of biological chemistry Medium 21212262
2012 Mst1 and Mst2 control thymic egress and T cell migration by activating Rho GTPases Rac1 and RhoA. MST1/2-deficient SP thymocytes show abolished sphingosine-1-phosphate- and CCL21-induced Mob1 phosphorylation, Rac1/RhoA GTP charging, and cell migration. When phosphorylated by Mst1/Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8. Mst1/2 double-knockout hematopoietic cells, Mob1 phosphorylation assays, Rac1/RhoA GTP charging assays, Dock8 co-immunoprecipitation with phospho-Mob1, migration assays The Journal of experimental medicine High 22412158
2014 MST1 is activated under diabetogenic conditions in beta cells and directly phosphorylates the beta cell transcription factor PDX1 at Thr11, causing PDX1 ubiquitination and proteasomal degradation, leading to impaired insulin secretion. MST1 also induces mitochondria-dependent apoptosis through upregulation of BIM (BH3-only protein). MST1 deficiency restores normoglycemia and beta cell function in vivo. In vitro kinase assay (MST1 phosphorylation of PDX1 at T11), ubiquitination assay, MST1 knockout/transgenic mouse models, islet apoptosis assays Nature medicine High 24633305
2014 Mst1 promotes cardiac myocyte apoptosis through a K-Ras/RASSF1A/Mst1 complex localized to mitochondria in response to oxidative stress. Activated Mst1 phosphorylates Bcl-xL at Ser14 (within the BH4 domain), antagonizing Bcl-xL-Bax binding and causing Bax activation and mitochondria-mediated apoptosis. In vitro kinase assay (Mst1 phosphorylation of Bcl-xL at Ser14), co-immunoprecipitation of K-Ras/RASSF1A/Mst1 complex, mitochondrial fractionation, Bax activation assay, cardiac myocyte apoptosis assay Molecular cell High 24813943
2014 The MST1/2-SAV1 complex promotes ciliogenesis. MST1 localizes to the basal body of cilia and is activated during ciliogenesis. MST1/2 binds and phosphorylates Aurora kinase A (AURKA), leading to dissociation of the AURKA/HDAC6 cilia-disassembly complex. MST1/2-SAV1 also associates with the NPHP transition-zone complex, promoting ciliary localization of ciliary cargoes. MST1/2 or SAV1 depletion in cultured cells and zebrafish, immunolocalization to basal body, in vitro kinase assay (MST1 phosphorylation of AURKA), co-immunoprecipitation with AURKA/HDAC6 and NPHP complex Nature communications High 25367221
2015 Mst1 and Mst2 positively regulate phagocytic ROS production by controlling mitochondrial trafficking to phagosomes. Mst1/2 activate the GTPase Rac to promote TLR-triggered assembly of the TRAF6-ECSIT complex required for mitochondrial recruitment to phagosomes. Inactive Rac2(D57N) disrupts the TRAF6-ECSIT complex by sequestering TRAF6. Mst1/2 knockout macrophages, Rac activation assays, TRAF6-ECSIT co-immunoprecipitation, mitochondrion-phagosome colocalization imaging, ROS measurement, bactericidal assays Nature immunology High 26414765
2015 mTORC2 (Rictor complex) directly phosphorylates MST1 at Ser438 in the SARAH domain, thereby reducing MST1 homodimerization and kinase activity. Cardiac-specific mTORC2 disruption (Rictor deletion) causes marked activation of MST1, leading to cardiac dysfunction and dilation under pressure overload. In vitro kinase assay (mTORC2 phosphorylation of MST1 at S438), site-directed mutagenesis, cardiac-specific Rictor KO mice, MST1 dimerization and activity assays Cell reports High 25843706
2016 Mst1 shuts off cytosolic antiviral defense by directly associating with IRF3 and phosphorylating it at Thr75 and Thr253, abolishing activated IRF3 homodimerization, chromatin occupancy, and IRF3-mediated transcription. Mst1 also impedes virus-induced TBK1 activation, further attenuating IRF3 activation. Mst1 depletion or ablation enhances antiviral response. Mst2 does not have this effect. Functional kinome screen, in vitro kinase assay (MST1 phosphorylation of IRF3 at T75/T253), co-immunoprecipitation (MST1-IRF3), IRF3 homodimerization assay, chromatin occupancy assay, MST1 KO mice with viral challenge Genes & development High 27125670
2016 DLG5 functions as an evolutionarily conserved scaffold that links MST1/2 with Par-1 polarity proteins (MARK1/2/3), inhibiting MST1/2 kinase activity and the MST1/2-LATS1/2 association. Hippo signaling is hyperactive in Dlg5-/- tissues; conditional deletion of Mst1/2 fully rescues the phenotypes of brain-specific Dlg5-KO mice. Affinity purification/mass spectrometry, MST1/2 kinase activity assay in DLG5-null cells, genetic rescue (Mst1/2 conditional deletion in Dlg5-KO), co-immunoprecipitation Genes & development High 28087714
2016 H-ras promotes formation of inactive Mst1/Mst2 heterodimers via an Erk-dependent mechanism. Mst1/Mst2 heterodimerize in cells through SARAH domains, and these heterodimers have much-reduced kinase activity compared to Mst1 or Mst2 homodimers. Cells lacking Mst1 are resistant to H-ras-mediated transformation and maintain active Hippo pathway signaling. Co-immunoprecipitation of Mst1/Mst2 heterodimers, SARAH domain deletion/mutation, kinase activity assay of hetero- vs. homodimers, H-ras transformation assays, Mst1-KO cells Current biology : CB High 27238285
2016 Pharmacological inhibition of MST1/2 with XMU-MP-1 (a selective, reversible inhibitor) blocks MST1/2 kinase activities, thereby activating downstream YAP and promoting cell growth. Co-crystal structure confirmed XMU-MP-1 binds on-target to MST1/2. XMU-MP-1 augments intestinal and liver repair/regeneration in mouse models. ELISA-based high-throughput biochemical kinase assay, co-crystal structure of XMU-MP-1 with MST1/2, structure-activity relationship, in vivo pharmacokinetics, mouse injury models Science translational medicine High 27535619
2016 Mst1 kinase phosphorylates the actin-bundling protein L-plastin (LPL) at Thr89 in vitro, and Mst1 interacts with LPL in cells. Mutation of Thr89 to Ala impairs LPL localization to lamellipodia and fails to restore T cell migration in LPL-deficient cells or rescue thymic egress in bone marrow chimeras. In vitro kinase assay (MST1 phosphorylation of LPL at T89), co-immunoprecipitation, T89A mutant expression, T cell migration assays, bone marrow chimeras Journal of immunology High 27465533
2017 Rassf1A and Rassf5 modulate MST1 activity via SARAH domain heterodimerization; the MST1 N-terminal kinase domain also plays a role in stabilizing the complex beyond SARAH-SARAH interaction. Rassf-MST1 complex positively regulates MST1-H2B Ser14 phosphorylation (chromatin condensation marker) while suppressing MST1-FoxO phosphorylation. Surface plasmon resonance (domain mapping), in vitro kinase assays (H2B and FoxO phosphorylation by MST1 in presence/absence of Rassf), domain deletion/mutagenesis Scientific reports Medium 28327630
2018 MST1 is a component of the TNFα receptor 1 signaling complex (TNF-RSC). TNFα induces MST1 recruitment to TNF-RSC and interaction with HOIP (catalytic LUBAC component). Activated MST1 phosphorylates HOIP, inhibiting LUBAC-dependent linear ubiquitination of NEMO/IKKγ, thereby attenuating TNFα-induced NF-κB signaling. MST1 genetic ablation potentiates IKK activity and NF-κB target gene expression. Co-immunoprecipitation of MST1 with TNF-RSC, in vitro kinase assay (MST1 phosphorylation of HOIP), LUBAC ubiquitination assay, MST1 KO MEFs and macrophages, NF-κB reporter and cytokine assays Molecular cell High 30901564
2018 MST1/2 act as signal-dependent amplifiers of IL-2-STAT5 activity in regulatory T cells. Unbiased quantitative proteomics revealed MST1 association with the cytoskeletal DOCK8-LRCHs module. MST1 deficiency limits Treg cell migration, access to IL-2, and activity of the small GTPase Rac, which mediates downstream STAT5 activation. Conditional Mst1/Mst2 KO in Treg cells, quantitative proteomics (AP-MS), Rac GTPase activity assay, STAT5 phosphorylation assay, Treg migration assays, IL-2 signaling assays Immunity High 30413360
2019 MST1 directly phosphorylates and binds the netrin receptor UNC5B at Thr428, promoting its apoptotic activation and dopaminergic neuronal loss in the context of Netrin1 reduction. MST1 activation by Netrin1 deprivation diminishes YAP levels and increases cell death. Knockout of UNC5B abolishes netrin depletion-induced dopaminergic loss; blockade of MST1-UNC5B phosphorylation suppresses neuronal apoptosis. In vitro kinase assay (MST1 phosphorylation of UNC5B at T428), co-immunoprecipitation (MST1-UNC5B), UNC5B knockout, phospho-specific antibody, dopaminergic neuron apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 32929029
2019 MST1 directly phosphorylates Nur77 (nuclear receptor) at Thr366, promoting Nur77 transcriptional activity and upregulating downstream β3-integrin expression to improve endometrial receptivity. Endometrial phospho-Nur77 (T366) level is decreased in women with recurrent implantation failure. In vitro kinase assay followed by LC-MS/MS (identification of T366 phosphorylation site), phos-tag SDS-PAGE, phospho-specific antibody, luciferase transcriptional assay, embryo adhesion assay, delayed implantation mouse model EBioMedicine High 36623453
2019 Gemcitabine activates MST1 through ROS production in pancreatic cancer cells; activated MST1 translocates to mitochondria and forms a complex with cyclophilin D (Cyp-D). MST1/Cyp-D mitochondrial complexation is required for gemcitabine-induced cell death; cyclosporin A (Cyp-D inhibitor) prevents this complexation and cell death. Co-immunoprecipitation (MST1-CypD), mitochondrial fractionation, ROS assay, shRNA silencing of MST1/CypD, cyclosporin A treatment, cell death assays Biochimie Medium 24732633
2009 Akt phosphorylates MST1 at Thr120, inhibiting MST1 kinase activity, nuclear translocation, and autophosphorylation at Thr183. Phospho-T120 MST1 fails to activate downstream FOXO3a and JNK. An inverse correlation between pMST1-T120 and pMST1-T183 is observed in human ovarian tumors. In vitro kinase assay (Akt phosphorylation of MST1 at T120), T120 mutant analysis, Akt-MST1 co-immunoprecipitation, nuclear translocation assay, FOXO3a/JNK activation assays, human tumor analysis The Journal of biological chemistry High 19940129
2021 TRAF6 mediates LPS-induced ubiquitination of MST1/STK4 in macrophages, resulting in negative feedback regulation. MST1 inhibits TRAF6 autoubiquitination and TRAF6-mediated downstream NF-κB signaling. Myeloid-specific MST1 ablation enhances NF-κB activation and proinflammatory cytokine production after LPS, and increases susceptibility to LPS-induced septic shock. Myeloid-specific MST1 KO mice, ubiquitination assays, TRAF6 autoubiquitination assay, co-immunoprecipitation, NF-κB reporter, cytokine measurement, septic shock model Cellular and molecular life sciences : CMLS High 32975614
2022 MST1 directly phosphorylates p53, promoting neuronal apoptosis and Alzheimer's disease-like cognitive deficits. MST1 associates with p53; p53 knockout largely reverses MST1-induced AD-like cognitive deficits. Co-immunoprecipitation (MST1-p53), MST1 overexpression in normal and 5xFAD mice, p53 knockout rescue, cognitive and synaptic plasticity assays Progress in neurobiology Medium 35525373
2022 MST1 phosphorylates Cx43 (connexin 43) at Ser255 in endothelial cells; this phosphorylation closes Cx43 hemichannels and prevents EC activation. Oscillatory shear stress inhibits MST1 phosphorylation, leading to reduced pCx43-S255, Cx43 hemichannel opening (mediated by Filamin B-dependent translocation of Cx43 to lipid rafts), EC activation, and atherosclerosis. Mass spectrometry (substrate identification), Co-IP, proximity ligation assay, dye uptake assay (hemichannel function), lentiviral MST1/Cx43-S255 overexpression, EC-specific Mst1-KO/ApoE mice in carotid ligation atherosclerosis model Circulation research High 36164986
2019 MST1 suppresses pancreatic cancer via ROS-induced caspase-1-dependent pyroptosis. This mechanism is independent of the Hippo/YAP pathway; ROS scavenger N-acetylcysteine attenuates MST1-induced caspase-1 activation and cell death. MST1 overexpression in PDAC cells, caspase-1 activity assay, ROS measurement, N-acetylcysteine rescue, cell death/proliferation/migration/invasion assays, YAP pathway epistasis Molecular cancer research : MCR Medium 30796177
2016 MST1 negatively regulates Hippo signaling in dendritic cells through the p38 MAPK pathway: MST1 deficiency in DCs increases p38 MAPK activation, leading to increased IL-6 secretion and subsequent STAT3 activation in CD4+ T cells, promoting Th17 differentiation. DC-specific MST1 KO/overexpression, p38 MAPK activation assay, IL-6 ELISA, STAT3 activation assay, Th17 differentiation assay, EAE model Nature communications Medium 28145433
2019 FGFR4 phosphorylates MST1 at Tyr433 in a kinase activity-dependent manner (confirmed by mass spectrometry). Y433F mutation in MST1 induces MST1 activation (increased Thr phosphorylation of MST1/2 and MOB1). FGFR4 inhibition leads to increased MST1/2 activation, enhanced MST1 nuclear localization, and generation of cleaved/autophosphorylated MST1, and apoptosis. Kinase substrate screen, mass spectrometry (Y433 phosphorylation), Y433F mutagenesis, MST1/2/MOB1 phosphorylation assays, FGFR4 knockdown/inhibition, nuclear localization imaging Cell death and differentiation High 30903103
2024 SIRT7 suppresses MST1 through dual mechanisms: (1) transcriptional repression by binding the MST1 promoter and inducing H3K18 deacetylation, and (2) direct binding and deacetylation of MST1 protein, priming acetylation-dependent MST1 ubiquitination and proteasomal degradation. MST1 reduction promotes YAP nuclear localization and transcriptional activation in liver cancer. ChIP (SIRT7 on MST1 promoter, H3K18ac), co-immunoprecipitation (SIRT7-MST1), mass spectrometry (MST1 deacetylation sites), ubiquitination assay, luciferase (MST1 promoter activity), YAP nuclear localization assay, xenograft mouse model Cancer science High 38288904
2021 USP46 directly binds MST1 and decreases its ubiquitination (stabilizes MST1 protein), thereby potentiating MST1 kinase activity to suppress YAP1 and HCC progression. Co-immunoprecipitation (USP46-MST1), ubiquitination assay, MST1 protein stability assay, YAP1 activity assay, HCC cell proliferation/invasion, in vivo xenograft Experimental cell research Medium 34029571
2016 MST1 promotes Sirt1 stability by inhibiting Sirt1 ubiquitination in hepatocytes. Mst1-/- mice show impaired fasting-induced hepatic Sirt1 expression. MST1 overexpression inhibits Srebp-1c expression and increases antioxidant gene expression in primary hepatocytes. Mst1 knockout mice (fasting/HFD model), ubiquitination assay for Sirt1, Sirt1 and Srebp-1c western blot in primary hepatocytes with MST1 overexpression Biochemical and biophysical research communications Medium 26903296
2016 Mst1 regulates MST1-mediated endothelial tip cell polarity and sprouting angiogenesis via a ROS-MST1-FOXO1 cascade. Hypoxia activates MST1 through mitochondrial ROS; activated MST1 promotes FOXO1 nuclear import, augmenting transcription of polarity and migration-associated genes. Endothelial-specific MST1 or FOXO1 deletion mice, ROS measurement, MST1 kinase activation assay, FOXO1 nuclear translocation imaging, sprouting angiogenesis (retinal and OIR models) Nature communications High 30783090

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer cell 796 19878874
2010 Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proceedings of the National Academy of Sciences of the United States of America 474 20080598
2008 MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Current biology : CB 359 18328708
2016 Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Science translational medicine 332 27535619
1998 Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1. The EMBO journal 331 9545236
2015 Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nature immunology 212 26414765
1996 The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain. The Journal of biological chemistry 193 8702870
2014 MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nature medicine 182 24633305
2002 Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation. The Journal of biological chemistry 164 12223493
2009 Regulation of neuronal cell death by MST1-FOXO1 signaling. The Journal of biological chemistry 160 19221179
2019 Quercetin Suppresses the Progression of Atherosclerosis by Regulating MST1-Mediated Autophagy in ox-LDL-Induced RAW264.7 Macrophage Foam Cells. International journal of molecular sciences 151 31816893
2017 Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. Journal of pineal research 151 28480597
2001 Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proceedings of the National Academy of Sciences of the United States of America 147 11517310
2012 The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. The Journal of experimental medicine 142 22412158
2009 Mst1 controls lymphocyte trafficking and interstitial motility within lymph nodes. The EMBO journal 140 19339990
2008 The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proceedings of the National Academy of Sciences of the United States of America 134 19073936
2014 Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL. Molecular cell 124 24813943
2007 The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. The EMBO journal 118 17932490
2019 Mst1 inhibition attenuates non-alcoholic fatty liver disease via reversing Parkin-related mitophagy. Redox biology 117 30708325
2015 mTORC2 regulates cardiac response to stress by inhibiting MST1. Cell reports 116 25843706
2009 Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse. Molecular and cellular biology 115 19786569
2011 The c-Abl-MST1 signaling pathway mediates oxidative stress-induced neuronal cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience 111 21715626
2019 MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis. Molecular cancer research : MCR 110 30796177
2016 MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice. Diabetologia 108 27510910
2010 Mst1 is an interacting protein that mediates PHLPPs' induced apoptosis. Molecular cell 107 20513427
2018 Mst1 promotes cardiac ischemia-reperfusion injury by inhibiting the ERK-CREB pathway and repressing FUNDC1-mediated mitophagy. The journal of physiological sciences : JPS 104 29961191
2001 MST1-JNK promotes apoptosis via caspase-dependent and independent pathways. Genes to cells : devoted to molecular & cellular mechanisms 104 11442632
2018 Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R-STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity. Immunity 99 30413360
2010 Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development. British journal of cancer 92 21102585
2022 MST1 mediates neuronal loss and cognitive deficits: A novel therapeutic target for Alzheimer's disease. Progress in neurobiology 84 35525373
2018 Mst1 inhibits Sirt3 expression and contributes to diabetic cardiomyopathy through inhibiting Parkin-dependent mitophagy. Biochimica et biophysica acta. Molecular basis of disease 83 29674007
2011 MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation. The Journal of biological chemistry 83 21212262
2013 Mst1 and Mst2 kinases: regulations and diseases. Cell & bioscience 81 23985272
2018 Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy. Biochimica et biophysica acta. Molecular basis of disease 79 30251683
2002 Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis. The Journal of biological chemistry 78 12384512
2016 Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation. Genes & development 76 27125670
2016 MST1/MST2 Protein Kinases: Regulation and Physiologic Roles. Biochemistry 76 27618557
2019 A MST1-FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis. Nature communications 74 30783090
2004 Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene 74 15007383
2015 Hippo/MST1 signaling mediates microglial activation following acute cerebral ischemia-reperfusion injury. Brain, behavior, and immunity 72 26721416
2017 Dendritic cell MST1 inhibits Th17 differentiation. Nature communications 71 28145433
2014 The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nature communications 71 25367221
2008 Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal immunology 70 19079170
2009 Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120. The Journal of biological chemistry 68 19940129
2006 Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases. Methods in enzymology 67 16757333
2016 DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2. Genes & development 65 28087714
2018 Mst1 regulates post-infarction cardiac injury through the JNK-Drp1-mitochondrial fission pathway. Cellular & molecular biology letters 55 29760744
2019 MST1 Negatively Regulates TNFα-Induced NF-κB Signaling through Modulating LUBAC Activity. Molecular cell 54 30901564
2015 A conserved MST1/2-YAP axis mediates Hippo signaling during lung growth. Developmental biology 54 25912685
2020 Exosomal miR-199a-5p promotes hepatic lipid accumulation by modulating MST1 expression and fatty acid metabolism. Hepatology international 53 33037981
2018 Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage. Frontiers in molecular neuroscience 52 29632474
2016 Integrin α2β1 inhibits MST1 kinase phosphorylation and activates Yes-associated protein oncogenic signaling in hepatocellular carcinoma. Oncotarget 52 27765911
2020 Tubule-Specific Mst1/2 Deficiency Induces CKD via YAP and Non-YAP Mechanisms. Journal of the American Society of Nephrology : JASN 50 32253273
2019 FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis. Cell death and differentiation 49 30903103
2014 Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway. Journal of neuro-oncology 49 25373346
2016 MST1: a promising therapeutic target to restore functional beta cell mass in diabetes. Diabetologia 45 27053234
2010 MST1 limits the kinase activity of aurora B to promote stable kinetochore-microtubule attachment. Current biology : CB 43 20171103
2021 CCL2 regulation of MST1-mTOR-STAT1 signaling axis controls BCR signaling and B-cell differentiation. Cell death and differentiation 41 33879857
2020 Mst1 knockdown alleviates cardiac lipotoxicity and inhibits the development of diabetic cardiomyopathy in db/db mice. Biochimica et biophysica acta. Molecular basis of disease 41 32320827
2014 Genetic deletion of Mst1 alters T cell function and protects against autoimmunity. PloS one 41 24852423
2020 Netrin1 deficiency activates MST1 via UNC5B receptor, promoting dopaminergic apoptosis in Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 39 32929029
2014 Gemcitabine-induced pancreatic cancer cell death is associated with MST1/cyclophilin D mitochondrial complexation. Biochimie 39 24732633
2022 MST1 Suppresses Disturbed Flow Induced Atherosclerosis. Circulation research 37 36164986
2019 MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells. International journal of molecular sciences 37 31117242
2019 Mst1 deletion reduces septic cardiomyopathy via activating Parkin-related mitophagy. Journal of cellular physiology 34 31215035
2014 Overexpression of MYC and EZH2 cooperates to epigenetically silence MST1 expression. Epigenetics 34 24499724
2011 Cross-regulation between oncogenic BRAF(V600E) kinase and the MST1 pathway in papillary thyroid carcinoma. PloS one 34 21249150
2020 LncRNA SNHG17 knockdown promotes Parkin-dependent mitophagy and reduces apoptosis of podocytes through Mst1. Cell cycle (Georgetown, Tex.) 31 32627655
2016 Mst1 Kinase Regulates the Actin-Bundling Protein L-Plastin To Promote T Cell Migration. Journal of immunology (Baltimore, Md. : 1950) 31 27465533
2016 Mst1 regulates hepatic lipid metabolism by inhibiting Sirt1 ubiquitination in mice. Biochemical and biophysical research communications 30 26903296
2014 Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1 signalling. Cellular signalling 30 24747552
2024 SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1. Cancer science 29 38288904
2024 Inhibition of MST1 ameliorates neuronal apoptosis via GSK3β/β-TrCP/NRF2 pathway in spinal cord injury accompanied by diabetes. Redox biology 29 38430683
2022 Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer. Cancer cell international 29 35642057
2017 TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 28802229
2017 Understanding the role of mammalian sterile 20-like kinase 1 (MST1) in cardiovascular disorders. Journal of molecular and cellular cardiology 29 29155025
2018 Cardiac-specific Mst1 deficiency inhibits ROS-mediated JNK signalling to alleviate Ang II-induced cardiomyocyte apoptosis. Journal of cellular and molecular medicine 28 30338935
2021 Inhibitors of the Hippo Pathway Kinases STK3/MST2 and STK4/MST1 Have Utility for the Treatment of Acute Myeloid Leukemia. Journal of medicinal chemistry 26 34807584
2020 Hippo kinases MST1 and MST2 control the differentiation of the epididymal initial segment via the MEK-ERK pathway. Cell death and differentiation 26 32332916
2016 H-ras Inhibits the Hippo Pathway by Promoting Mst1/Mst2 Heterodimerization. Current biology : CB 26 27238285
2016 Mst1 positively regulates B-cell receptor signaling via CD19 transcriptional levels. Blood advances 26 29296937
2016 Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis. Experimental cell research 25 27793648
2021 Deubiquitinating enzyme USP46 suppresses the progression of hepatocellular carcinoma by stabilizing MST1. Experimental cell research 24 34029571
2018 Mst1/2 Kinases Modulate Glucose Uptake for Osteoblast Differentiation and Bone Formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 29474739
2017 Rassf Proteins as Modulators of Mst1 Kinase Activity. Scientific reports 24 28327630
2023 Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice. EBioMedicine 22 36623453
2020 SRV2 promotes mitochondrial fission and Mst1-Drp1 signaling in LPS-induced septic cardiomyopathy. Aging 22 31951593
2020 MST1/2 Balance Immune Activation and Tolerance by Orchestrating Adhesion, Transcription, and Organelle Dynamics in Lymphocytes. Frontiers in immunology 22 32435241
2019 Mst1 deletion reduces hyperglycemia-mediated vascular dysfunction via attenuating mitochondrial fission and modulating the JNK signaling pathway. Journal of cellular physiology 22 31206688
2018 Mst1 regulates non-small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/F‑actin pathways. International journal of oncology 22 30320378
2012 Tumor suppressor Hippo/MST1 kinase mediates chemotaxis by regulating spreading and adhesion. Proceedings of the National Academy of Sciences of the United States of America 21 22847424
2023 miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis. PeerJ 20 37727684
2020 Hippo Kinases MST1/2 Regulate Immune Cell Functions in Cancer, Infection, and Autoimmune Diseases. Critical reviews in eukaryotic gene expression 20 33389879
2014 Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. PloS one 20 25133611
2024 MST1/2: Important regulators of Hippo pathway in immune system associated diseases. Cancer letters 19 38369002
2022 XMU-MP-1 protects heart from ischemia/reperfusion injury in mice through modulating Mst1/AMPK pathway. European journal of pharmacology 19 35123978
2020 TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-κB signaling pathway in macrophages. Cellular and molecular life sciences : CMLS 19 32975614
2018 The Role of Mst1 in Lymphocyte Homeostasis and Function. Frontiers in immunology 19 29459865
2023 MST1/2 in inflammation and immunity. Cell adhesion & migration 18 37909712
2014 Mst1 and mst2 are essential regulators of trophoblast differentiation and placenta morphogenesis. PloS one 18 24595170

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