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First published on August 12, 2004; DOI: 10.1124/mol.104.004093

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Received for publication June 22, 2004.
Revised August 12, 2004.
Accepted for publication August 12, 2004.

Reciprocal signaling between the transcriptional co-factor Eya2 and specific members of the G{alpha}i family

Alan C. Embry 1, Jennifer L. Glick 2, Maurine E. Linder 3, Patrick J. Casey 1*

1 Duke University Medical Center 2 University of Washington 3 Washington University

* Address correspondence to: E-mail: casey006{at}mc.duke.edu

Abstract

As part of a program to elucidate signaling processes controlled by the heterotrimeric G protein G{alpha}z, a human fetal brain cDNA library was screened for proteins that specifically interact with the activated form of G{alpha}z. One of the most-encountered molecules in this screen was Eya2, a member of the eyes absent family of proteins. Mammalian Eya proteins are cytosolic proteins that are known to interact with members of the sine oculis (Six) family of homeodomain transcription factors. This interaction facilitates the translocation of Eya into the nucleus, where the Eya/Six complex regulates transcription during critical stages of embryonic development. In vitro binding studies confirmed that G{alpha}z interacts with Eya2 in an activation-dependent fashion; furthermore, most other members of the G{alpha}i family including G{alpha}i1, G{alpha}i2, and G{alpha}i3 were found to interact with Eya2. Interestingly, one of the most abundant G{alpha}i proteins, G{alpha}o, did not interact with Eya2. Co-expression of the activated forms of G{alpha}i1, G{alpha}i2, and G{alpha}i3, but not G{alpha}o, with Eya2 recruited Eya2 to the plasma membrane, prevented Eya2 translocation into the nucleus, and abrogated Eya2/Six4-mediated transcription. Additionally, Eya2 impinged on G protein-mediated signaling, as evidenced by its ability to relieve G{alpha}i2-mediated inhibition of adenylyl cyclase. These results demonstrate that the interaction between the G{alpha}i proteins and Eya2 may impact on seemingly disparate regulatory events involving both classes of proteins.


Key words: Gi family, cAMP, Transcriptional coactivators


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[Abstract] [Full Text] [PDF]


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