Fan W T, Koch C A, de Hoog C L, Fam N P, Moran M F
Banting and Best Department of Medical Research Department of Molecular and Medical Genetics University of Toronto Charles H. Best Institute 112 College Street, Toronto, M5G 1L6, Canada.
Curr Biol. 1998;8(16):935-8. doi: 10.1016/s0960-9822(07)00376-4.
Ras and Rac are membrane-associated GTPases that function as molecular switches activating intracellular mitogen-activated protein kinase (MAPK) cascades and other effector pathways in response to extracellular signals [1]. Activation of Ras and Rac into their GTP-bound conformations is directly controlled by specific guanine-nucleotide exchange factors (GEFs), which catalyze GDP release. Several Ras-specific GEFs that are related to the budding yeast protein Cdc25p have been described, whereas GEFs for Rac-related GTPases contain a region that is homologous to the oncoprotein DbI [2-3]. The Ras-GRF1 and Ras-GRF2 proteins, which couple Ras activation to serpentine receptors and calcium signals, contain both Cdc25 and DbI homology (DH) regions [3-4]. Here, we demonstrate that Ras-GRF2 is a bifunctional signaling protein that is able to bind and activate Ras and Rac, and thereby coordinate the activation of the extracellular-signal-regulated kinase (ERK) and stress-activated protein kinase (SAPK) pathways.
Ras和Rac是与膜相关的GTP酶，作为分子开关，响应细胞外信号激活细胞内丝裂原活化蛋白激酶（MAPK）级联反应和其他效应途径[1]。Ras和Rac激活为其GTP结合构象直接受特定鸟嘌呤核苷酸交换因子（GEF）控制，GEF催化GDP释放。已描述了几种与出芽酵母蛋白Cdc25p相关的Ras特异性GEF，而Rac相关GTP酶的GEF含有与癌蛋白DbI同源的区域[2-3]。将Ras激活与蛇形受体和钙信号偶联的Ras-GRF1和Ras-GRF2蛋白同时含有Cdc25和DbI同源（DH）区域[3-4]。在此，我们证明Ras-GRF2是一种双功能信号蛋白，能够结合并激活Ras和Rac，从而协调细胞外信号调节激酶（ERK）和应激激活蛋白激酶（SAPK）途径的激活。
