Schubbert Suzanne, Bollag Gideon, Lyubynska Natalya, Nguyen Hoa, Kratz Christian P, Zenker Martin, Niemeyer Charlotte M, Molven Anders, Shannon Kevin
Department of Pediatrics, University of California, 513 Parnassus Avenue, HSE 302, San Francisco, California 94143, USA.
Mol Cell Biol. 2007 Nov;27(22):7765-70. doi: 10.1128/MCB.00965-07. Epub 2007 Sep 17.
Germ line missense mutations in HRAS and KRAS and in genes encoding molecules that function up- or downstream of Ras in cellular signaling networks cause a group of related developmental disorders that includes Costello syndrome, Noonan syndrome, and cardiofaciocutaneous syndrome. We performed detailed biochemical and functional studies of three mutant K-Ras proteins (P34R, D153V, and F156L) found in individuals with Noonan syndrome and cardiofaciocutaneous syndrome. Mutant K-Ras proteins demonstrate a range of gain-of-function effects in different cell types, and biochemical analysis supports the idea that the intrinsic Ras guanosine nucleotide triphosphatase (GTPase) activity, the responsiveness of these proteins to GTPase-activating proteins, and guanine nucleotide dissociation all regulate developmental programs in vivo.
HRAS和KRAS以及细胞信号网络中Ras上下游功能分子编码基因的种系错义突变会导致一组相关的发育障碍，包括科斯特洛综合征、努南综合征和心脏颜面皮肤综合征。我们对在努南综合征和心脏颜面皮肤综合征患者中发现的三种突变型K-Ras蛋白（P34R、D153V和F156L）进行了详细的生化和功能研究。突变型K-Ras蛋白在不同细胞类型中表现出一系列功能获得效应，生化分析支持这样一种观点，即内在的Ras鸟苷三磷酸酶（GTPase）活性、这些蛋白对GTPase激活蛋白的反应性以及鸟嘌呤核苷酸解离均在体内调节发育程序。
