The transcription factor Eyes absent is a protein tyrosine phosphatase

Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localizatio...

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Bibliographic Details
Published in:	Nature Vol. 426; no. 6964; pp. 299 - 302
Main Authors:	Rebay, Ilaria, Tootle, Tina L, Silver, Serena J, Davies, Erin L, Newman, Victoria, Latek, Robert R, Mills, Ishara A, Selengut, Jeremy D, Parlikar, Beth E. W
Format:	Journal Article
Language:	English
Published:	London Nature Publishing 20-11-2003 Nature Publishing Group
Subjects:	Amino Acid Motifs Amino Acid Sequence Animals Antibodies, Phospho-Specific - immunology Biological and medical sciences Cell differentiation, maturation, development, hematopoiesis Cell physiology Drosophila Drosophila melanogaster - embryology Drosophila melanogaster - enzymology Drosophila melanogaster - genetics Drosophila Proteins - chemistry Drosophila Proteins - genetics Drosophila Proteins - metabolism Embryonic Induction Eye - embryology Eye - enzymology Eye - metabolism Eye Proteins - chemistry Eye Proteins - genetics Eye Proteins - metabolism Eyes & eyesight Fundamental and applied biological sciences. Psychology Gene Expression Regulation Kinetics Mice Models, Molecular Molecular and cellular biology Molecular Sequence Data Mutation - genetics Phosphorylation Protein Conformation Protein Tyrosine Phosphatases - chemistry Protein Tyrosine Phosphatases - genetics Protein Tyrosine Phosphatases - metabolism Proteins Substrate Specificity Transcription Factors - chemistry Transcription Factors - genetics Transcription Factors - metabolism Enzyme Insecta Phosphoric monoester hydrolases Esterases Drosophilidae Eye Arthropoda Development Hydrolases Invertebrata Transcription factor Mechanism of action Drosophila melanogaster Diptera Protein-tyrosine-phosphatase
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Summary:	Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0028-0836 1476-4687
DOI:	10.1038/nature02097