Eyes absent represents a class of protein tyrosine phosphatases

• Published in: Nature 2003-11, Vol.426 (6964), p.295-298
• Main Authors: Hegde, Rashmi S, Rayapureddi, Jayanagendra P, Kattamuri, Chandramohan, Steinmetz, Brian D, Frankfort, Benjamin J, Ostrin, Edwin J, Mardon, Graeme
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Cataracts; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Drosophila melanogaster - embryology; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - chemistry; Drosophila Proteins - metabolism; Eye - embryology; Eye - enzymology; Eye - metabolism; Eye Proteins - antagonists & inhibitors; Eye Proteins - chemistry; Eye Proteins - metabolism; Eyes & eyesight; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; letter; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Mutation; Phosphorylation; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - metabolism; Proteins; Science; Science (multidisciplinary); Substrate Specificity
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02093

The Eyes absent proteins are members of a conserved regulatory network implicated in the development of the eye, muscle, kidney and ear. Mutations in the Eyes absent genes have been associated with several congenital disorders including the multi-organ disease bronchio-oto-renal syndrome, congenital cataracts and late-onset deafness. 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) proteins. 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 intermediate. 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.