Eyes absent represents a class of protein tyrosine phosphatases

Jayanagendra P. Rayapureddi, Chandramohan Kattamuri, Brian D. Steinmetz, Benjamin J. Frankfort, Edwin J. Ostrin, Graeme Mardon and Rashmi S. Hegde ()
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Jayanagendra P. Rayapureddi: Cincinnati Childrens Hospital Research Foundation
Chandramohan Kattamuri: Cincinnati Childrens Hospital Research Foundation
Brian D. Steinmetz: Cincinnati Childrens Hospital Research Foundation
Benjamin J. Frankfort: Neuroscience and Program in Developmental Biology, Baylor College of Medicine
Edwin J. Ostrin: Neuroscience and Program in Developmental Biology, Baylor College of Medicine
Graeme Mardon: Neuroscience and Program in Developmental Biology, Baylor College of Medicine
Rashmi S. Hegde: Cincinnati Childrens Hospital Research Foundation

Nature, 2003, vol. 426, issue 6964, 295-298

Abstract: 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.

Date: 2003
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DOI: 10.1038/nature02093

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