Soderling Scott H, Binns Kathleen L, Wayman Gary A, Davee Stephen M, Ong Siew Hwa, Pawson Tony, Scott John D
Howard Hughes Medical Institute, Vollum Institute, 3181 Sam Jackson Park Road, Portland, Oregon 97239-3098, USA.
Nat Cell Biol. 2002 Dec;4(12):970-5. doi: 10.1038/ncb886.
WAVE-1, which is also known as Scar, is a scaffolding protein that directs actin reorganization by relaying signals from the GTPase Rac to the Arp2/3 complex. Although the molecular details of WAVE activation by Rac have been described, the mechanisms by which these signals are terminated remain unknown. Here we have used tandem mass spectrometry to identify previously unknown components of the WAVE signalling network including WRP, a Rac-selective GTPase-activating protein. WRP binds directly to WAVE-1 through its Src homology domain 3 and specifically inhibits Rac function in vivo. Thus, we propose that WRP is a binding partner of WAVE-1 that functions as a signal termination factor for Rac.
WAVE-1，也被称为Scar，是一种支架蛋白，它通过将信号从GTP酶Rac传递到Arp2/3复合物来指导肌动蛋白重组。尽管已经描述了Rac激活WAVE的分子细节，但这些信号终止的机制仍然未知。在这里，我们使用串联质谱法来鉴定WAVE信号网络中以前未知的成分，包括WRP，一种Rac选择性GTP酶激活蛋白。WRP通过其Src同源结构域3直接与WAVE-1结合，并在体内特异性抑制Rac功能。因此，我们提出WRP是WAVE-1的结合伙伴，作为Rac的信号终止因子发挥作用。
