TY - JOUR
T1 - Eyes absent represents a class of protein tyrosine phosphatases
AU - Rayapureddi, Jayanagendra P.
AU - Kattamuri, Chandramohan
AU - Steinmetz, Brian D.
AU - Frankfort, Benjamin J.
AU - Ostrin, Edwin J.
AU - Mardon, Graeme
AU - Hegde, Rashmi S.
N1 - Funding Information:
Acknowledgements We thank R. Menon, Y.-J. Li, S. McKinnon, Z. Jorai, J. Kargel,T. Shipman, J.-L. Pitetti and the genomic platform of the Frontiers in Genetics at the National Center of Competence in Research for technical assistance; all members of the Parada laboratory for discussions; A. McMahon, R. Behringer, K. Parker, R. Lovell-Badge and J. Dean for probes; and J. Wilson, K. Parker, J. Graff, J. Goldstein and G. Karsenty for critically reading the manuscript. This work was funded by an Excellence in Education Endowment to L.F.P.
PY - 2003/11/20
Y1 - 2003/11/20
N2 - 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.
AB - 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.
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U2 - 10.1038/nature02093
DO - 10.1038/nature02093
M3 - Article
C2 - 14628052
AN - SCOPUS:0344443179
SN - 0028-0836
VL - 426
SP - 295
EP - 298
JO - Nature
JF - Nature
IS - 6964
ER -