Ligeti Erzsébet, Dagher Marie-Claire, Hernandez Samuel E, Koleske Anthony J, Settleman Jeffrey
Department of Physiology, Semmelweis University, 1444 Budapest, Hungary.
J Biol Chem. 2004 Feb 13;279(7):5055-8. doi: 10.1074/jbc.C300547200. Epub 2003 Dec 29.
The major cellular inhibitors of the small GTPases of the Ras superfamily are the GTPase-activating proteins (GAPs), which stimulate the intrinsic GTP hydrolyzing activity of GTPases, thereby inactivating them. The catalytic activity of several GAPs is reportedly inhibited or stimulated by various phospholipids and fatty acids in vitro, indicating a likely physiological role for lipids in regulating small GTPases. We find that the p190 RhoGAP, a potent GAP for the Rho and Rac GTPases, is similarly sensitive to phospholipids. Interestingly, however, several of the tested phospholipids were found to effectively inhibit the RhoGAP activity of p190 but stimulate its RacGAP activity. Thus, phospholipids have the ability to "switch" the GTPase substrate preference of a GAP, thereby providing a novel regulatory mechanism for the small GTPases.
Ras超家族小GTP酶的主要细胞内抑制剂是GTP酶激活蛋白（GAP），它刺激GTP酶的内在GTP水解活性，从而使其失活。据报道，几种GAP的催化活性在体外受到各种磷脂和脂肪酸的抑制或刺激，表明脂质在调节小GTP酶方面可能具有生理作用。我们发现p190 RhoGAP（一种对Rho和Rac GTP酶有效的GAP）同样对磷脂敏感。然而，有趣的是，发现几种经测试的磷脂能有效抑制p190的RhoGAP活性，但能刺激其RacGAP活性。因此，磷脂有能力“切换”GAP的GTP酶底物偏好，从而为小GTP酶提供一种新的调节机制。
