Principles of Cell Signaling and Biological Consequences
Student #7 Response to Student #6
19 May 2005
Cross-talk between the EGF receptor and Notch signaling pathways has been documented previously, although the mechanism is poorly understood. Gro is a corepressor that acts with a variety of repressors, including effectors of the Notch, Wnt, and TGF-B pathways. It had been shown previously that there are genetic interactions between Gro and EGFR pathway, so the authors examine cross-talk between the EGFR and Notch pathways via Gro activity. They see an increase in Gro phosphorylation with a constitutively active EGFR, or constitutively active MAPK. They also showed that Gro was directly phosphorylated by MAPK in a kinase assay. This phosphorylation of Gro decreases its ability as a repressor, and suggests that RTK signaling may downregulate Gro repressor activity. It had been shown that there is cross-talk between EGFR and Notch pathways during vein formation in wing patterning. The authors see that expression of Gro that is nonphosphorylated results in a loss of veins in the wing, while expression of constitutively pseudo-phosphorylated Gro resulted in ectopic vein material. This suggested that cross-talk between EGFR and Notch can occur at the level of Gro in this process. They also see that phosphorylation of Gro plays a role in bristle formation, and suggest that regulation of Gro by EGFR is a basis for antagonism of Notch signaling. The data suggest that Gro is a point of intersection between the EGFR and Notch pathways. Downregulation of Gro by RTK phosphorylation would allow the RTK pathway to alter transcriptional activity, so this paper shows how modification of a corepressor can link signaling and transcriptional activity. I agree with student's assessment that the paper does demonstrate cross-talk between two signaling pathways, and also demonstrates the functional consequences of this cross-talk.
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882