CDK5 interacts with MST2 and modulates the Hippo signalling pathway
MST2 (STK3) is a major upstream kinase in the Hippo signalling pathway, an evolutionary conserved pathway in regulation of organ size, self‐renewal and tissue homeostasis. Its downstream effectors are the transcriptional regulators YAP and TAZ. This pathway is regulated by a variety of factors, such...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13962 |
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| author | Mehak Passi Jan B. Stöckl Thomas Fröhlich Simone Moser Angelika M. Vollmar Stefan Zahler |
| author_facet | Mehak Passi Jan B. Stöckl Thomas Fröhlich Simone Moser Angelika M. Vollmar Stefan Zahler |
| author_sort | Mehak Passi |
| collection | DOAJ |
| description | MST2 (STK3) is a major upstream kinase in the Hippo signalling pathway, an evolutionary conserved pathway in regulation of organ size, self‐renewal and tissue homeostasis. Its downstream effectors are the transcriptional regulators YAP and TAZ. This pathway is regulated by a variety of factors, such as substrate stiffness or cell–cell contacts. Using a yeast two‐hybrid screen, we detected a novel interaction between the kinases MST2 and CDK5, which we further confirmed by co‐immunoprecipitation experiments. Cyclin‐dependent kinase 5 (CDK5) is an unusual member of the family of cyclin‐dependent kinases, involved in tumour growth and angiogenesis. Although a link between CDK5 and Hippo has been previously postulated, the mode of action is still elusive. Here, we show that knockdown of CDK5 causes reduced transcriptional activity of YAP and that CDK5 influences the phosphorylation levels of the Hippo upstream kinase LATS1. Moreover, a phosphoproteomics approach revealed that CDK5 interferes with the phosphorylation of DLG5, another upstream kinase, which regulates the Hippo pathway. Hence, CDK5 seems to act as a signalling hub for integrating the Hippo pathway and other signalling cascades. These interactions might have important implications for the use of CDK5 inhibitors, which are already in clinical use for tumour diseases. |
| format | Article |
| id | doaj-art-6efaa78147c64a8b9d69f01237c207b6 |
| institution | OA Journals |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-6efaa78147c64a8b9d69f01237c207b62025-08-20T01:55:37ZengWileyFEBS Open Bio2211-54632025-04-0115464766010.1002/2211-5463.13962CDK5 interacts with MST2 and modulates the Hippo signalling pathwayMehak Passi0Jan B. Stöckl1Thomas Fröhlich2Simone Moser3Angelika M. Vollmar4Stefan Zahler5Center for Drug Research Ludwig‐Maximilians‐University Munich GermanyLaboratory for Functional Genome Analysis, Gene Center Munich Ludwig‐Maximilians‐University Munich GermanyLaboratory for Functional Genome Analysis, Gene Center Munich Ludwig‐Maximilians‐University Munich GermanyCenter for Drug Research Ludwig‐Maximilians‐University Munich GermanyCenter for Drug Research Ludwig‐Maximilians‐University Munich GermanyCenter for Drug Research Ludwig‐Maximilians‐University Munich GermanyMST2 (STK3) is a major upstream kinase in the Hippo signalling pathway, an evolutionary conserved pathway in regulation of organ size, self‐renewal and tissue homeostasis. Its downstream effectors are the transcriptional regulators YAP and TAZ. This pathway is regulated by a variety of factors, such as substrate stiffness or cell–cell contacts. Using a yeast two‐hybrid screen, we detected a novel interaction between the kinases MST2 and CDK5, which we further confirmed by co‐immunoprecipitation experiments. Cyclin‐dependent kinase 5 (CDK5) is an unusual member of the family of cyclin‐dependent kinases, involved in tumour growth and angiogenesis. Although a link between CDK5 and Hippo has been previously postulated, the mode of action is still elusive. Here, we show that knockdown of CDK5 causes reduced transcriptional activity of YAP and that CDK5 influences the phosphorylation levels of the Hippo upstream kinase LATS1. Moreover, a phosphoproteomics approach revealed that CDK5 interferes with the phosphorylation of DLG5, another upstream kinase, which regulates the Hippo pathway. Hence, CDK5 seems to act as a signalling hub for integrating the Hippo pathway and other signalling cascades. These interactions might have important implications for the use of CDK5 inhibitors, which are already in clinical use for tumour diseases.https://doi.org/10.1002/2211-5463.13962CDK5HippoTAZYAPyeast‐two‐hybrid |
| spellingShingle | Mehak Passi Jan B. Stöckl Thomas Fröhlich Simone Moser Angelika M. Vollmar Stefan Zahler CDK5 interacts with MST2 and modulates the Hippo signalling pathway FEBS Open Bio CDK5 Hippo TAZ YAP yeast‐two‐hybrid |
| title | CDK5 interacts with MST2 and modulates the Hippo signalling pathway |
| title_full | CDK5 interacts with MST2 and modulates the Hippo signalling pathway |
| title_fullStr | CDK5 interacts with MST2 and modulates the Hippo signalling pathway |
| title_full_unstemmed | CDK5 interacts with MST2 and modulates the Hippo signalling pathway |
| title_short | CDK5 interacts with MST2 and modulates the Hippo signalling pathway |
| title_sort | cdk5 interacts with mst2 and modulates the hippo signalling pathway |
| topic | CDK5 Hippo TAZ YAP yeast‐two‐hybrid |
| url | https://doi.org/10.1002/2211-5463.13962 |
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