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First published online 23 January 2008
doi: 10.1242/dev.015206

Development 135, 829-837 (2008)
Published by The Company of Biologists 2008
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Multiple RTK pathways downregulate Groucho-mediated repression in Drosophila embryogenesis

Einat Cinnamon1, Aharon Helman1, Rachel Ben-Haroush Schyr2, Amir Orian3, Gerardo Jiménez4 and Ze'ev Paroush1,*

1 Department of Biochemistry, Faculty of Medicine, The Hebrew University, PO Box 12272, Jerusalem 91120, Israel.
2 Department of Cellular Biochemistry and Human Genetics, Faculty of Medicine, The Hebrew University, PO Box 12272, Jerusalem 91120, Israel.
3 The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
4 Institut de Biologia Molecular de Barcelona-CSIC and Institució Catalana de Recerca i Estudis Avançats, Parc Científic de Barcelona, 08028-Barcelona, Spain.

* Author for correspondence (e-mail: zparoush{at}cc.huji.ac.il)

Accepted 12 December 2007

RTK pathways establish cell fates in a wide range of developmental processes. However, how the pathway effector MAPK coordinately regulates the expression of multiple target genes is not fully understood. We have previously shown that the EGFR RTK pathway causes phosphorylation and downregulation of Groucho, a global co-repressor that is widely used by many developmentally important repressors for silencing their various targets. Here, we use specific antibodies that reveal the dynamics of Groucho phosphorylation by MAPK, and show that Groucho is phosphorylated in response to several RTK pathways during Drosophila embryogenesis. Focusing on the regulation of terminal patterning by the Torso RTK pathway, we demonstrate that attenuation of Groucho's repressor function via phosphorylation is essential for the transcriptional output of the pathway and for terminal cell specification. Importantly, Groucho is phosphorylated by an efficient mechanism that does not alter its subcellular localisation or decrease its stability; rather, modified Groucho endures long after MAPK activation has terminated. We propose that phosphorylation of Groucho provides a widespread, long-term mechanism by which RTK signals control target gene expression.

Key words: Drosophila, Groucho, TLE, phosphorylation, RTK signalling, Repression






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