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Sci. Signal., 24 February 2009
Vol. 2, Issue 59, p. ec72
[DOI: 10.1126/scisignal.259ec72]

EDITORS' CHOICE

Cell Biology Both a Transcription Factor and a Phosphatase

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

The transcriptional coactivator eyes absent (Eya) is critical to Drosophila eye development; its misexpression elicits ectopic eye formation, whereas its loss leads to eyeless flies. In addition to acting as a transcription factor, Eya has tyrosine phosphatase activity; however, the relationship between these two functions has been unclear. Noting that Eya is itself subject to tyrosine phosphorylation, Xiong et al. searched for genetic interactions between Eya and a tyrosine kinase and identified cooperative interactions between Eya and the Abelson (Abl) nonreceptor tyrosine kinase. For example, loss of Abl function suppressed ectopic eye induction by Eya, and a dominant-negative Abl mutant inhibited rescue by Eya of the Eya loss-of-function eyeless phenotype. Abl and Eya cooperated to regulate axon targeting in the embryonic Drosophila central nervous system and in the larval brain. Coexpression of wild-type, but not catalytically inactive, Abl increased Eya tyrosine phosphorylation in cultured S2 cells, as did their co-overexpression in developing Drosophila tissues; in vitro kinase assays indicated that Abl phosphorylated Eya directly. Drosophila Abl is a membrane-associated cytoplasmic kinase, and coexpression of wild-type (but not catalytically inactive) Abl promoted Eya relocalization from the nucleus to the cytoplasm. Analyses of transgenic lines in which Eya was restricted to the nucleus indicated that its cytoplasmic location was functionally important; similarly, experiments with cytoplasmically targeted Eya confirmed its critical role in the nucleus. Coexpression of two spatially distinct pools of Eya, one targeted to the cytoplasm and the other to the nucleus, reconstituted Eya function, indicating that these two pools were functionally distinct. Coexpression of a catalytically inactive Eya mutant targeted to the cytoplasm with wild-type Eya in the nucleus indicated that Eya phosphatase activity was critical to its cytoplasmic function. The authors thus propose that, in addition to its role as a transcription factor in the nucleus, Eya is recruited to the cytoplasm, where it has a distinct role as a phosphatase, through Abl-mediated phosphorylation.

W. Xiong, N. M. Dabbouseh, I. Rebay, Interactions with the Abelson tyrosine kinase reveal compartmentalization of eyes absent function between nucleus and cytoplasm. Dev. Cell 16, 271–279 (2009). [PubMed]

Citation: E. M. Adler, Both a Transcription Factor and a Phosphatase. Sci. Signal. 2, ec72 (2009).



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