ArticleCancer research2010
Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
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Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- A Number of the N-terminal RASSF Family: RASSF7.Anti-cancer agents in medicinal chemistry · 2024Pooled it
- Pooled it
- Rigosertib Reverses Hypertrophic Cardiomyopathy in Noonan Syndrome.Circulation · 2026Article
- PRIP/PLCL deficiency activates PI3K-AKT-YAP signaling and promotes organ fibrosis.Cell communication and signaling : CCS · 2026Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- MST2 Acts via AKT Activity to Promote Neurite Outgrowth and Functional Recovery after Spinal Cord Injury in Mice.Molecular neurobiology · 2024Article
- Rac1 GTPase Regulates the βTrCP-Mediated Proteolysis of YAP Independently of the LATS1/2 Kinases.Cancers · 2024Article
- Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Molecular mechanisms involved in regulating protein activity and biological function of MST3.Cell division · 2023Review
- RAF1 deficiency causes a lethal syndrome that underscores RTK signaling during embryogenesis.EMBO molecular medicine · 2023Article
- The hippo kinases MST1/2 in cardiovascular and metabolic diseases: A promising therapeutic target option for pharmacotherapy.Acta pharmaceutica Sinica. B · 2023Review
- The potential role of Hippo pathway regulates cellular metabolism via signaling crosstalk in disease-induced macrophage polarization.Frontiers in immunology · 2023Review
- Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway.Molecular medicine reports · 2023Article
- Article
- Interaction of LATS1 with SMAC links the MST2/Hippo pathway with apoptosis in an IAP-dependent manner.Cell death & disease · 2022Article
- Interplay of Developmental Hippo-Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer.Cells · 2022Review
- Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival.Circulation research · 2022Article
- Targeting Akt in cancer for precision therapy.Journal of hematology & oncology · 2021Review
- Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network.International journal of molecular sciences · 2021Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian MST kinases function in stress-induced apoptosis to limit tumor progression. However, there is limited understanding about MST2 control by key regulators of cell division and survival. Raf-1 binds and inhibits MST2 kinase, whereas dissociation from Raf-1 and binding to tumor suppressor protein RASSF1A activates MST2. Akt phosphorylates MST2 in response to mitogens, oncogenic Ras, or depletion of tumor suppressor phosphatase and tensin homologue deleted on chromosome 10. We identified T117 and T384 as Akt phosphorylation sites in MST2. Mutation of these sites inhibited MST2 binding to Raf-1 kinase but enhanced binding to tumor suppressor RASSF1A, accentuating downstream c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase signaling and promoting apoptosis. We determined that MST2 phosphorylation by Akt limits MST2 activity in two ways: first, by blocking its binding to RASSF1A and by promoting its association into the Raf-1 inhibitory complex, and second, by preventing homodimerization of MST2, which is needed for its activation. Dissociation of the Raf-1-MST2 complex promoted mitogenic signaling and coordinately licensed apoptotic risk. Using Ras effector domain mutants, we found that Akt is essential to prevent MST2 activation after mitogenic stimulation. Our findings elucidate how MST2 serves as a hub to integrate biological outputs of the Raf-1 and Akt pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.