Liu K, Li G
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA.
J Biol Chem. 1998 Apr 24;273(17):10087-90. doi: 10.1074/jbc.273.17.10087.
Ras is a master GTPase switch controlling multiple signal transduction cascades in the regulation of cell proliferation and differentiation. Rab5 is a local GTPase switch that is localized on early endosomes and controls early endosome fusion. This study demonstrates that the catalytic domain of p120 GTPase-activating protein (GAP), a well known Ras GAP, is able to interact physically with Rab5 and stimulate its GTPase activity. This GAP activity toward Rab5, however, cannot be extended to other Rab GTPases such as Rab3, Rab4, and Rab6, indicating that it is not a generic GAP for the Rab family of GTPases that regulate intracellular membrane fusion during endocytosis and exocytosis. The findings indicate a level of structural similarity between Ras and Rab5 unexpected from their primary sequences. They also suggest a possible signal transduction regulation of the Rab5-dependent endosome fusion via the Ras GAP.
Ras是一种主要的GTP酶开关，在细胞增殖和分化的调控中控制多个信号转导级联反应。Rab5是一种定位在早期内体上的局部GTP酶开关，控制早期内体融合。本研究表明，著名的Ras GTP酶激活蛋白（GAP）p120的催化结构域能够与Rab5发生物理相互作用，并刺激其GTP酶活性。然而，这种针对Rab5的GAP活性不能扩展到其他Rab GTP酶，如Rab3、Rab4和Rab6，这表明它不是调节内吞作用和外排作用期间细胞内膜融合的Rab GTP酶家族的通用GAP。这些发现表明Ras和Rab5之间存在一定程度的结构相似性，这从它们的一级序列中是意想不到的。它们还提示了通过Ras GAP对Rab5依赖性内体融合进行信号转导调控的可能性。
