The Eyes Absent Family of Phosphotyrosine Phosphatases: Properties and Roles in Developmental Regulation of Transcription

Abstract

Integration of multiple signaling pathways at the level of their transcriptional effectors provides an important strategy for fine-tuning gene expression and ensuring a proper program of development. Posttranslational modifications, such as phosphorylation, play important roles in modulating transcription factor activity. The discovery that the transcription factor Eyes absent (Eya) possesses protein phosphatase activity provides an interesting new paradigm. Eya may regulate the phosphorylation state of either itself or its transcriptional cofactors, thereby directly affecting transcriptional output. The identification of a growing number of transcription factors with enzymic activity suggests that such dual-function proteins exert greater control of signaling events than previously imagined. Given the conservation of both its phosphatase and transcription factor activity across mammalian species, Eya provides an excellent model for studying how a single protein integrates these two functions under the influence of multiple signaling pathways to promote development.