Journal
EMBO JOURNAL
Volume 25, Issue 1, Pages 70-79Publisher
WILEY
DOI: 10.1038/sj.emboj.7600924
Keywords
ETS-family transcription factors; Mae; MAPK; pnt-p2; SAM domain; transcriptional regulation
Categories
Funding
- NCI NIH HHS [R01 CA081000, R01-CA081000, R01 CA081000-09, R01 CA081000-06, R01 CA081000-08, R01 CA081000-07, R01 CA081000-05] Funding Source: Medline
- NIGMS NIH HHS [R01 GM044522, R01-GM44522] Funding Source: Medline
Ask authors/readers for more resources
During Drosophila melanogaster eye development, signaling through receptor tyrosine kinases (RTKs) leads to activation of a mitogen activated protein tyrosine kinase, called Rolled. Key nuclear targets of Rolled are two antagonistic transcription factors: Yan, a repressor, and Pointed-P2 (Pnt-P2), an activator. A critical regulator of this process, Mae, can interact with both Yan and Pnt-P2 through their SAM domains. Although earlier work showed that Mae derepresses Yan-regulated transcription by depolymerizing the Yan polymer, the mechanism of Pnt-P2 regulation by Mae remained undefined. We find that efficient phosphorylation and consequent activation of Pnt-P2 requires a three-dimensional docking surface on its SAM domain for the MAP kinase, Rolled. Mae binding to Pnt-P2 occludes this docking surface, thereby acting to downregulate Pnt-P2 activity. Docking site blocking provides a new mechanism whereby the cell can precisely modulate kinase signaling at specific targets, providing another layer of regulation beyond the more global changes effected by alterations in the activity of the kinase itself.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available