GTPase-activating proteins or GTPase-accelerating proteins (GAPs) are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event. [1] .

RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities: Inactivation of Ras from its active GTP-bound form to its inactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain

对Ras-GAP复合物的三维结构的测定和对Ras突变形式的测试解释了令人困惑的观察结果，即大多数致癌、构成活性Ras蛋白（ RasD ）在12位点突变。用任何其他氨基酸（脯氨酸除外）取代正常的甘氨酸12可以阻断GAP蛋白的功能结合，并在本质上“锁定”Ras在活性的GTP ...

1997年2月1日 · Upon activation of many growth factor receptors, Ras-GAP becomes phosphorylated and associates with cytosolic proteins as well as with the autophosphorylated tyrosine kinase receptors. Ras-GAP has been shown to form complexes with two other phosphoproteins, a p62 and a p190 protein (Table 1).

2023年9月8日 · Using the optimized reaction paths, we devised a fast and accurate procedure to design GAP mutants that activate G12D Ras. We replaced GAP residues near the active site and determined the activation barrier for 190 single mutants.

Regulation of Ras GTPases by GTPase-activating proteins (GAPs) is essential for their normal signaling. Nine of the ten GAPs for Ras contain a C2 domain immediately proximal to their canonical GAP domain, and in RasGAP (p120GAP, p120RasGAP; RASA1) mutation of this domain is associated with vascular malformations in humans.Here, we show that the C2 domain of RasGAP is required for full ...

Recently, RAS GTPase Activating Proteins (RAS GAPs) have emerged as an expanding class of tumor suppressors that, when inactivated, provide an alternative mechanism of activating RAS. RAS GAPs normally turn off RAS by catalyzing the hydrolysis of RAS-GTP.

2009年3月1日 · Several members of the Ras superfamily share the ability to bind and hydrolyze GTP. Ras switches between an active (GTP-bound) and an inactive (GDP-bound) state. This cycle is critical and is controlled by guanine exchange factor …

1997年6月23日 · GTPase-activating proteins (GAPs) accelerate the very slow intrinsic hydrolysis reaction of the GTP-bound Ras by several orders of magnitude and thereby act as presumably negative regulators of Ras action. The GTP hydrolysis of oncogenic mutants of …

1997年7月18日 · The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations.