Show simple item record

dc.contributor.authorEichhorn, Pieter
dc.contributor.authorCreyghton, M.P.
dc.contributor.authorWilhelmsen, K.
dc.contributor.authorVan Dam, H.
dc.contributor.authorBernards, R.
dc.date.accessioned2020-12-03T02:53:44Z
dc.date.available2020-12-03T02:53:44Z
dc.date.issued2007
dc.identifier.citationEichhorn, P.J.A. and Creyghton, M.P. and Wilhelmsen, K. and Van Dam, H. and Bernards, R. 2007. A RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC. PLoS Genetics. 3 (12): pp. 2381-2394.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/81903
dc.identifier.doi10.1371/journal.pgen.0030218
dc.description.abstract

© 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.

dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectGenetics & Heredity
dc.subjectGROWTH-FACTOR RECEPTOR
dc.subjectN-TERMINAL KINASE
dc.subjectADENOVIRUS E4ORF4 PROTEIN
dc.subjectMIDDLE TUMOR-ANTIGEN
dc.subjectOKADAIC ACID
dc.subjectBREAST-CANCER
dc.subjectSERINE/THREONINE PHOSPHATASE
dc.subjectSIGNAL-TRANSDUCTION
dc.subjectCSF-1 RECEPTOR
dc.subjectCELL-GROWTH
dc.titleA RNA interference screen identifies the protein phosphatase 2A subunit PR55γ as a stress-sensitive inhibitor of c-SRC
dc.typeJournal Article
dcterms.source.volume3
dcterms.source.number12
dcterms.source.startPage2381
dcterms.source.endPage2394
dcterms.source.issn1553-7390
dcterms.source.titlePLoS Genetics
dc.date.updated2020-12-03T02:53:41Z
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusOpen access
curtin.facultyFaculty of Health Sciences
curtin.contributor.orcidEichhorn, Pieter [0000-0001-5840-943X]
curtin.identifier.article-numberARTN e218
dcterms.source.eissn1553-7404
curtin.contributor.scopusauthoridEichhorn, Pieter [7004166602]


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/