Journal article
Protein phosphatase PP2Cα S-glutathionylation regulates cell migration
The Journal of biological chemistry, v 300(10), 107784
18 Sep 2024
PMID: 39303918
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Redox signaling is a fundamental mechanism that controls all major biological processes partly via protein cysteine oxidations, including S-glutathionylation. Despite over 2,000 cysteines identified to form S-glutathionylation in databases, the identification of redox cysteines functionally linked to a biological process of interest remains challenging. Here, we demonstrate a strategy combining glutathionylation proteomic database, bioinformatics, and biological screening, which resulted in the identification of S-glutathionylated proteins, including PP2Cα, as redox players of cell migration. We showed that PP2Cα, a prototypical magnesium-dependent serine/threonine phosphatase, is susceptible to S-glutathionylation selectively at non-conserved C314. PP2Cα glutathionylation causes increased migration and invasion of breast cancer cell lines in oxidative stress or upon hydrogen peroxide production. Mechanistically, PP2Cα glutathionylation modulates its protein-protein interactions, activating c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways to elevate migration and invasion. In addition, PP2Cα glutathionylation occurs in response to epidermal-growth factor, supporting a serine/threonine phosphatase PP2Cα as a new redox player in growth factor signal transduction.
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Details
- Title
- Protein phosphatase PP2Cα S-glutathionylation regulates cell migration
- Creators
- Dhanushika S.K. Kukulage - Drexel UniversityKusal T.G. Samarasinghe - AmgenNadee N.J. Matarage Don - Drexel UniversityMadhu C. Shivamadhu - Department of Chemistry, Drexel University, Philadelphia, PA 19104, USAKyosuke Shishikura - University of PennsylvaniaWilliam Schiff - Drexel UniversityFaezeh Mashhadi Ramezani - Department of Chemistry, Drexel University, Philadelphia, PA 19104, USARayavarapu Padmavathi - Drexel UniversityMegan L. Matthews - University of PennsylvaniaYoung-Hoon Ahn - Department of Chemistry, Drexel University, Philadelphia, PA 19104, USA
- Publication Details
- The Journal of biological chemistry, v 300(10), 107784
- Publisher
- Elsevier; AMSTERDAM
- Number of pages
- 18
- Grant note
- National Institutes of Health (NIH): R01 HL131740, R01 GM143214
Funding and additional information - The research was supported by grants from the National Institutes of Health (NIH) , R01 HL131740 (Y.-H. A.) and R01 GM143214 (Y.-H. A.) and the research fund from Drexel University. The content is solely the responsibility of the authors and does not necessarily represent the of fi cial views of the National Institutes of Health.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:001337164000001
- Scopus ID
- 2-s2.0-85206180158
- Other Identifier
- 991021905013104721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology