ArticleThe Journal of biological chemistry2010
Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway activity via maintenance of protein phosphatase-2A catalytic subunit levels and consequent suppression of inhibitory Raf-1 phosphorylation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Decreased PP2A expression and activity represent a therapeutic target for plexiform neurofibroma.Acta neuropathologica communications · 2026Article
- Phosphorylation-dependent regulation of Eleven Lysine Rich Leukemia (ELL) uncovered by quantitative global phosphoproteomic analysis.Molecular genetics and genomics : MGG · 2026Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- The Diagnostic Potential ofFrontiers in oncology · 2022Article
- The RASSF1A Tumor Suppressor Binds the RasGAP DAB2IP and Modulates RAS Activation in Lung Cancer.Cancers · 2020Article
- Signaling pathways and clinical application of RASSF1A and SHOX2 in lung cancer.Journal of cancer research and clinical oncology · 2020Review
- Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Low‑frequency ultrasound and microbubbles combined with simvastatin promote the apoptosis of MCF‑7 cells by affecting the LATS1/YAP/RHAMM pathway.Molecular medicine reports · 2018Article
- RASSF1A Deficiency Enhances RAS-Driven Lung Tumorigenesis.Cancer research · 2018Article
- The polarity protein Angiomotin p130 controls dendritic spine maturation.The Journal of cell biology · 2018Article
- Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis.Experimental & molecular medicine · 2017Article
- MST1/MST2 Protein Kinases: Regulation and Physiologic Roles.Biochemistry · 2016Review
- Review
- Regulation of mammalian Ste20 (Mst) kinases.Trends in biochemical sciences · 2015Review
- Genetic variants in the Hippo pathway predict biochemical recurrence after radical prostatectomy for localized prostate cancer.Scientific reports · 2015Article
- Competing to coordinate cell fate decisions: the MST2-Raf-1 signaling device.Cell cycle (Georgetown, Tex.) · 2015Article
- The mammalian Ste20-like kinase 2 (Mst2) modulates stress-induced cardiac hypertrophy.The Journal of biological chemistry · 2014Article
- Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas.Lung cancer (Amsterdam, Netherlands) · 2014Article
- RASSF1A inactivation unleashes a tumor suppressor/oncogene cascade with context-dependent consequences on cell cycle progression.Molecular and cellular biology · 2014Article
- Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling.Cell & bioscience · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Many tumor suppressor proteins act to blunt the effects of mitogenic signaling pathways. Loss of function mutations in the merlin tumor suppressor underlie neurofibromatosis type 2 (NF2), a familial autosomal dominant cancer syndrome. Studies of Drosophila suggest that Hippo (hpo) is required for inhibition of cell proliferation mediated by dMer, the orthologue of human merlin. Mammalian sterile 20-like kinase-2 (Mst2) is a mammalian Hpo orthologue, and numerous studies implicate Mst2 as a tumor suppressor. Mst2 is negatively regulated by the proto-oncoprotein Raf-1 in a manner independent of the kinase activity of Raf-1. We sought to determine whether, in mammalian cells, merlin could positively regulate Mst2. We also sought to determine whether Mst2, in addition to being negatively regulated by Raf-1, might itself reciprocally regulate Raf-1. In contrast to findings from Drosophila, we find no evidence that mammalian merlin positively regulates mammalian Mst2. Instead, surprisingly, RNA interference silencing of Mst2 leads to elevated inhibitory phosphorylation of Raf-1 at Ser-259 and impaired Raf-1 kinase activity. Consequent to this, ERK pathway activation and cell proliferation are attenuated. Phosphatase-2A (PP2A) dephosphorylates Raf-1 Ser-259 in response to mitogens. Interestingly RNA interference silencing of Mst2 triggers a striking proteasome-dependent decrease in the levels of the catalytic subunit of PP2A (PP2A-C). A similar effect is achieved upon silencing of large tumor suppressor (LATS)-1 and LATS2, direct substrates of Mst2. Our studies reveal a more complex role for Mst2 than previously thought. The Mst2 --> LATS1/2 pathway, by maintaining PP2A-C levels, may, in some situations, positively affect mitogenic signaling.
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