Abstract
As part of a program to elucidate signaling processes controlled by the heterotrimeric G protein Gαz, a human fetal brain cDNA library was screened for proteins that specifically interact with the activated form of Gαz. One of the most-encountered molecules in this screen was Eya2, a member of the Eyes absent family of proteins. Mammalian Eya proteins are predominantly 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 Gαz interacts with Eya2 in an activation-dependent fashion; furthermore, most other members of the Gαi family including Gαi1, Gαi2, and Gαi3 were found to interact with Eya2. It is interesting that one of the most abundant Gαi proteins, Gαo, did not interact with Eya2. Coexpression of the activated forms of Gαi1, Gαi2, and Gαi3, but not Gαo, with Eya2 recruited Eya2 to the plasma membrane, prevented Eya2 translocation into the nucleus, and abrogated Eya2/Six4-mediated transcription. In addition, Eya2 impinged on G protein-mediated signaling, as evidenced by its ability to relieve Gαi2-mediated inhibition of adenylyl cyclase. These results demonstrate that the interaction between the Gαi proteins and Eya2 may impact on seemingly disparate regulatory events involving both classes of proteins.
- Received June 21, 2004.
- Accepted August 12, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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