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Principles of Cell Signaling and Biological Consequences

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Final Forum: Student #6

10 May 2005


Hasson et al. EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional Notch transcriptional output. 2005 Nature Genetics pp101-105. [PubMed] [Online Journal]

Antagonism between EGFR and Notch pathways is well documented but the level/junction at which crosstalk occurs has yet been fully understood. Price et al, in 1997, reported genetic interactions between Groucho (Gro) and signaling components of EGFR pathways, and postulated that Gro, being a co-repressor may be involved in the antagonistic interaction between EGFR and Notch signaling. In the paper highlighted, Hasson et al, using both biochemical procedures and mutagenesis, showed that Gro, indeed, serves as a junction for the interaction between EGFR and Notch pathways. In addition, they showed that in response to MAPK, phosphorylation of Gro leads to a decrease in Gro repressing capacity. With prior knowledge that EGFR pathway antagonizes Notch pathways in wing patterning and that Gro and its repressor partner, Notch effector E(spl)mbeta, are antivein determinants while EGFR pathway promotes vein formation by overriding these activity, the authors generated mutant flies that have either GroAA -- a stronger repressor, or GroDD -- a weak repressor when compared to wildtype, and examined the functional relevance of the crosstalk between these two pathways at the level/junction of Gro. The study showed that with a stronger repressor, there is a lack of vein formation in the drosophila wing disc while flies with the weak repressor have enriched vein formation. These findings clearly demonstrate the importance of crosstalk between two pathways in ensuring that the outcomes of downstream signaling leads to normal development and that a change in this junction will lead to dire functional consequences.

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