Journal article
The transcription factor Eyes absent is a protein tyrosine phosphatase
Nature (London), Vol.426(6964), pp.299-302
2003
DOI: 10.1038/nature02097
PMID: 14628053
Abstract
Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.
Details
- Title: Subtitle
- The transcription factor Eyes absent is a protein tyrosine phosphatase
- Creators
- Tina L TOOTLE - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesSerena J SLIVER - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesErin L DAVIES - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesVictoria NEWMAN - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesRobert R LATEK - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesIshara A MILLS - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesJeremy D SELENGUT - The Institute for Genomic Research, Rockville, Maryland 20850, United StatesBeth E. W PARLIKAR - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United StatesIlaria REBAY - Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, United States
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.426(6964), pp.299-302
- Publisher
- Nature Publishing; London
- DOI
- 10.1038/nature02097
- PMID
- 14628053
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 2003
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984025359402771
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