TY - JOUR
T1 - Geminin and Brahma act antagonistically to regulate EGFR-Ras-MAPK signaling in Drosophila
AU - Herr, Anabel
AU - Mckenzie, Lisa
AU - Suryadinata, Randy
AU - Sadowski, Martin
AU - Parsons, Linda M
AU - Sarcevic, Boris
AU - Richardson, Helena
PY - 2010
Y1 - 2010
N2 - Geminin was identified in Xenopus as a dual function protein involved in the regulation of DNA replication and neural differentiation. In Xenopus, Geminin acts to antagonize the Brahma (Brill) chromatin-remodeling protein, Brg1, during neural differentiation Here. we investigate the interaction of Geminin with the Brm complex during Drosophila development. We demonstrate that Drosophila Geminin (Gem) interacts antagonistically with the Brm-BAP complex during wing development Moreover, we show in vivo during wing development and biochemically that Brm acts to promote EGFR-Ras-MAPK signaling, as indicated by its effects on pERK levels, while Gem opposes this Furthermore, gem and brm alleles modulate the wing phenotype of a Raf gain-of-function mutant and the eye phenotype of a EGFR gain-of-function mutant Western analysis revealed that Gem over-expression in a background compromised for Brill function reduces Mek (MAPKK/Sor) protein levels, consistent with the decrease in ERK activation observed. Taken together, our results show that Gem and Brm act antagonistically to modulate the EGFR-Ras-MAPK signaling pathway, by affecting Mek levels during Drosophila development.
AB - Geminin was identified in Xenopus as a dual function protein involved in the regulation of DNA replication and neural differentiation. In Xenopus, Geminin acts to antagonize the Brahma (Brill) chromatin-remodeling protein, Brg1, during neural differentiation Here. we investigate the interaction of Geminin with the Brm complex during Drosophila development. We demonstrate that Drosophila Geminin (Gem) interacts antagonistically with the Brm-BAP complex during wing development Moreover, we show in vivo during wing development and biochemically that Brm acts to promote EGFR-Ras-MAPK signaling, as indicated by its effects on pERK levels, while Gem opposes this Furthermore, gem and brm alleles modulate the wing phenotype of a Raf gain-of-function mutant and the eye phenotype of a EGFR gain-of-function mutant Western analysis revealed that Gem over-expression in a background compromised for Brill function reduces Mek (MAPKK/Sor) protein levels, consistent with the decrease in ERK activation observed. Taken together, our results show that Gem and Brm act antagonistically to modulate the EGFR-Ras-MAPK signaling pathway, by affecting Mek levels during Drosophila development.
UR - http://www.sciencedirect.com/science/article/pii/S0012160610002368
U2 - 10.1016/j.ydbio.2010.04.006
DO - 10.1016/j.ydbio.2010.04.006
M3 - Article
SN - 0012-1606
VL - 344
SP - 36
EP - 51
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -