The <em>Aspergillus nidulans</em> MAPK Module AnSte11-Ste50-Ste7-Fus3 Controls Development and Secondary Metabolism

The sexual Fus3 MAP kinase module of yeast is highly conserved in eukaryotes and transmits external signals from the plasma membrane to the nucleus. We show here that the module of the filamentous fungus Aspergillus nidulans (An) consists of the AnFus3 MAP kinase, the upstream kinases AnSte7 and AnSte11, and the AnSte50 adaptor. The fungal MAPK module controls the coordination of fungal development and secondary metabolite production. It lacks the membrane docking yeast Ste5 scaffold homolog; but, similar to yeast, the entire MAPK module's proteins interact with each other at the plasma membrane. AnFus3 is the only subunit with the potential to enter the nucleus from the nuclear envelope. AnFus3 interacts with the conserved nuclear transcription factor AnSte12 to initiate sexual development and phosphorylates VeA, which is a major regulatory protein required for sexual development and coordinated secondary metabolite production. Our data suggest that not only Fus3, but even the entire MAPK module complex of four physically interacting proteins, can migrate from plasma membrane to nuclear envelope.酿酒酵母的有性生殖相关Fus3丝裂原活化蛋白激酶（MAP kinase）模块在真核生物中高度保守，可将胞外信号从质膜传递至细胞核。本研究显示，丝状真菌构巢曲霉（Aspergillus nidulans，简称An）的该模块由AnFus3丝裂原活化蛋白激酶、上游激酶AnSte7、AnSte11以及接头蛋白AnSte50组成。该真菌MAPK模块负责调控真菌发育与次级代谢产物合成的协同过程。其缺少与酿酒酵母Ste5支架蛋白同源的膜锚定蛋白；但与酿酒酵母类似，整个MAPK模块的所有蛋白均能在质膜处相互结合。AnFus3是该模块中唯一能够从核被膜进入细胞核的亚基。AnFus3可与保守的核转录因子AnSte12结合以启动有性生殖过程，并磷酸化VeA——VeA是调控有性生殖与次级代谢产物协同合成的关键调控蛋白。本研究数据表明，不仅Fus3，甚至由四个物理互作蛋白组成的完整MAPK模块复合物，均可从质膜迁移至核被膜。