Mondal Subhanjan, Bakthavatsalam Deenadayalan, Steimle Paul, Gassen Berthold, Rivero Francisco, Noegel Angelika A
Centre for Biochemistry, Institute of Biochemistry I, Medical Faculty and Centre for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany.
J Cell Biol. 2008 Jun 2;181(5):747-60. doi: 10.1083/jcb.200710111. Epub 2008 May 26.
Ras guanine nucleotide exchange factor (GEF) Q, a nucleotide exchange factor from Dictyostelium discoideum, is a 143-kD protein containing RasGEF domains and a DEP domain. We show that RasGEF Q can bind to F-actin, has the potential to form complexes with myosin heavy chain kinase (MHCK) A that contain active RasB, and is the predominant exchange factor for RasB. Overexpression of the RasGEF Q GEF domain activates RasB, causes enhanced recruitment of MHCK A to the cortex, and leads to cytokinesis defects in suspension, phenocopying cells expressing constitutively active RasB, and myosin-null mutants. RasGEF Q(-) mutants have defects in cell sorting and slug migration during later stages of development, in addition to cell polarity defects. Furthermore, RasGEF Q(-) mutants have increased levels of unphosphorylated myosin II, resulting in myosin II overassembly. Collectively, our results suggest that starvation signals through RasGEF Q to activate RasB, which then regulates processes requiring myosin II.
Ras鸟嘌呤核苷酸交换因子（GEF）Q是一种来自盘基网柄菌的核苷酸交换因子，是一种含有RasGEF结构域和DEP结构域的143-kD蛋白。我们发现RasGEF Q能与F-肌动蛋白结合，有潜力与包含活性RasB的肌球蛋白重链激酶（MHCK）A形成复合物，并且是RasB的主要交换因子。RasGEF Q的GEF结构域过表达会激活RasB，导致更多的MHCK A募集到皮层，并在悬浮培养中导致胞质分裂缺陷，模拟组成型活性RasB表达细胞和肌球蛋白缺失突变体的表型。RasGEF Q（-）突变体在发育后期的细胞分选和蛞蝓体迁移方面存在缺陷，此外还有细胞极性缺陷。此外，RasGEF Q（-）突变体中未磷酸化的肌球蛋白II水平升高，导致肌球蛋白II过度组装。总体而言，我们的结果表明饥饿信号通过RasGEF Q激活RasB，进而调节需要肌球蛋白II的过程。
