The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway

被引:226
作者
Bhattacharyya, RP
Reményi, A
Good, MC
Bashor, CJ
Falick, AM
Lim, WA
机构
[1] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Program Biol Sci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94143 USA
[4] Univ Calif Berkeley, Howard Hughes Med Inst, Mass Spectrometry Lab, Berkeley, CA 94720 USA
关键词
D O I
10.1126/science.1120941
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active-it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory rote, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.
引用
收藏
页码:822 / 826
页数:5
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