Premium
Mae inhibits Pointed‐P2 transcriptional activity by blocking its MAPK docking site
Author(s) -
Qiao Feng,
Harada Bryan,
Song Haiyun,
Whitelegge Julian,
Courey Albert J,
Bowie James U
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600924
Subject(s) - biology , docking (animal) , blocking (statistics) , computational biology , mapk/erk pathway , microbiology and biotechnology , phosphorylation , computer science , medicine , computer network , nursing
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.