A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC
© 2007 Eichhorn et al. Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogeneinduced signaling. Since most studies on the role of...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Language: | English |
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PUBLIC LIBRARY SCIENCE
2007
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/81903 |
| _version_ | 1848764442577207296 |
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| author | Eichhorn, Pieter Creyghton, M.P. Wilhelmsen, K. Van Dam, H. Bernards, R. |
| author_facet | Eichhorn, Pieter Creyghton, M.P. Wilhelmsen, K. Van Dam, H. Bernards, R. |
| author_sort | Eichhorn, Pieter |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2007 Eichhorn et al.
Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogeneinduced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55γ and PR55δ as inhibitors of c-Jun NH 2-terminal kinase (JNK) activation by UV irradiation. We show that PR55γ binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55γ and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55γ. |
| first_indexed | 2025-11-14T11:19:25Z |
| format | Journal Article |
| id | curtin-20.500.11937-81903 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:19:25Z |
| publishDate | 2007 |
| publisher | PUBLIC LIBRARY SCIENCE |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-819032021-01-08T05:04:21Z A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC Eichhorn, Pieter Creyghton, M.P. Wilhelmsen, K. Van Dam, H. Bernards, R. Science & Technology Life Sciences & Biomedicine Genetics & Heredity GROWTH-FACTOR RECEPTOR N-TERMINAL KINASE ADENOVIRUS E4ORF4 PROTEIN MIDDLE TUMOR-ANTIGEN OKADAIC ACID BREAST-CANCER SERINE/THREONINE PHOSPHATASE SIGNAL-TRANSDUCTION CSF-1 RECEPTOR CELL-GROWTH © 2007 Eichhorn et al. Protein Phosphatase type 2A (PP2A) represents a family of holoenzyme complexes with diverse biological activities. Specific holoenzyme complexes are thought to be deregulated during oncogenic transformation and oncogeneinduced signaling. Since most studies on the role of this phosphatase family have relied on the use of generic PP2A inhibitors, the contribution of individual PP2A holoenzyme complexes in PP2A-controlled signaling pathways is largely unclear. To gain insight into this, we have constructed a set of shRNA vectors targeting the individual PP2A regulatory subunits for suppression by RNA interference. Here, we identify PR55γ and PR55δ as inhibitors of c-Jun NH 2-terminal kinase (JNK) activation by UV irradiation. We show that PR55γ binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC. We also find that the physical interaction between PR55γ and c-SRC is sensitive to UV irradiation. Our data reveal a novel mechanism of c-SRC regulation whereby in response to stress c-SRC activity is regulated, at least in part, through loss of the interaction with its inhibitor, PR55γ. 2007 Journal Article http://hdl.handle.net/20.500.11937/81903 10.1371/journal.pgen.0030218 English http://creativecommons.org/licenses/by/4.0/ PUBLIC LIBRARY SCIENCE fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Genetics & Heredity GROWTH-FACTOR RECEPTOR N-TERMINAL KINASE ADENOVIRUS E4ORF4 PROTEIN MIDDLE TUMOR-ANTIGEN OKADAIC ACID BREAST-CANCER SERINE/THREONINE PHOSPHATASE SIGNAL-TRANSDUCTION CSF-1 RECEPTOR CELL-GROWTH Eichhorn, Pieter Creyghton, M.P. Wilhelmsen, K. Van Dam, H. Bernards, R. A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC |
| title | A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC |
| title_full | A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC |
| title_fullStr | A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC |
| title_full_unstemmed | A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC |
| title_short | A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC |
| title_sort | rna interference screen identifies the protein phosphatase 2a subunit pr55γ as a stress-sensitive inhibitor of c-src |
| topic | Science & Technology Life Sciences & Biomedicine Genetics & Heredity GROWTH-FACTOR RECEPTOR N-TERMINAL KINASE ADENOVIRUS E4ORF4 PROTEIN MIDDLE TUMOR-ANTIGEN OKADAIC ACID BREAST-CANCER SERINE/THREONINE PHOSPHATASE SIGNAL-TRANSDUCTION CSF-1 RECEPTOR CELL-GROWTH |
| url | http://hdl.handle.net/20.500.11937/81903 |