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Letters to Nature
Nature 426, 295-298 (20 November 2003) | doi:10.1038/nature02093; Received 28 May 2003; Accepted 10 September 2003
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Eyes absent represents a class of protein tyrosine phosphatases
Jayanagendra P. Rayapureddi1, Chandramohan Kattamuri1, Brian D. Steinmetz1, Benjamin J. Frankfort2,3, Edwin J. Ostrin2,3, Graeme Mardon2,4 & Rashmi S. Hegde1
- Division of Developmental Biology, Cincinnati Childrens Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
- Departments of Molecular and Human Genetics, Neuroscience and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
- Pathology, Neuroscience and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
- Ophthalmology, Neuroscience and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Correspondence to: Rashmi S. Hegde1 Email: rashmi.hegde@cchmc.org
Abstract
The Eyes absent proteins are members of a conserved regulatory network implicated in the development of the eye, muscle, kidney and ear1, 2, 3, 4, 5, 6, 7. Mutations in the Eyes absent genes have been associated with several congenital disorders including the multi-organ disease bronchio-oto-renal syndrome8, congenital cataracts9 and late-onset deafness10. On the basis of previous analyses it has been shown that Eyes absent is a nuclear transcription factor, acting through interaction with homeodomain-containing Sine oculis (also known as Six) proteins11. Here we show that Eyes absent is also a protein tyrosine phosphatase. It does not resemble the classical tyrosine phosphatases that use cysteine as a nucleophile and proceed by means of a thiol-phosphate intermediate12. Rather, Eyes absent is the prototype for a class of protein tyrosine phosphatases that use a nucleophilic aspartic acid in a metal-dependent reaction. Furthermore, the phosphatase activity of Eyes absent contributes to its ability to induce eye formation in Drosophila.
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