RRC ID 1586
Author Embry AC, Glick JL, Linder ME, Casey PJ.
Title Reciprocal signaling between the transcriptional co-factor Eya2 and specific members of the Galphai family.
Journal Mol. Pharmacol.
Abstract As part of a program to elucidate signaling processes controlled by the heterotrimeric G protein Galphaz, a human fetal brain cDNA library was screened for proteins that specifically interact with the activated form of Galphaz. 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 Galphaz interacts with Eya2 in an activation-dependent fashion; furthermore, most other members of the Galphai family including Galphai1, Galphai2, and Galphai3 were found to interact with Eya2. It is interesting that one of the most abundant Galphai proteins, Galphao, did not interact with Eya2. Coexpression of the activated forms of Galphai1, Galphai2, and Galphai3, but not Galphao, 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 Galphai2-mediated inhibition of adenylyl cyclase. These results demonstrate that the interaction between the Galphai proteins and Eya2 may impact on seemingly disparate regulatory events involving both classes of proteins.
Volume 66(5)
Pages 1325-31
Published 2004-11
DOI 10.1124/mol.104.004093
PII mol.104.004093
PMID 15308761
MeSH Adenylyl Cyclase Inhibitors Adenylyl Cyclases / metabolism Animals Cell Membrane / metabolism Cells, Cultured GTP-Binding Protein alpha Subunits, Gi-Go / metabolism* Heterotrimeric GTP-Binding Proteins / metabolism Homeodomain Proteins / metabolism Humans Intracellular Signaling Peptides and Proteins Nuclear Proteins Protein Tyrosine Phosphatases Trans-Activators / metabolism* Transcription Factors / metabolism* Transcriptional Activation / physiology
IF 3.853
Times Cited 16
WOS Category PHARMACOLOGY & PHARMACY
Resource
DNA material Six4 (M8 type) (RDB01774) Six4 (M18 type) (RDB01775) Six4 (SM type) (RDB01776)