Different structural organization of Ras and Rho effector domains.
Different structural organization of Ras and Rho effector domains.
复制标题
Ras 和 Rho 效应域的不同结构组织。
作者：
A. Self;H. Paterson;A. Hall
RAS调节细胞内的增殖和分化信号，该蛋白的激活可导致恶性转化。相关蛋白Rho的激活会影响细胞的形态，有人认为它也可能具有一定的致癌潜力。我们在这里表明，Rho不会在NIH3T3细胞中诱导恶性表型，相反，它是肌动蛋白应激纤维形成的有效激活剂。RAS和RHO之间有限的同源性使我们能够利用嵌合体来确定指定不同生物学活性的氨基酸和GTP酶激活蛋白(GAP)蛋白的敏感性。Rho被RAS的23-46位氨基酸取代，在NIH3T3单层中诱导转化灶，我们得出结论，RAS具有下游信号所需的单一效应结构域。虽然Rho的突变分析表明32-42位残基也是其生物学活性所必需的，但用Rho的25-48位氨基酸取代RAS并不能诱导肌动蛋白应激纤维的形成。在这些实验的基础上，我们提出Rho可能有两个效应域：一个在氨基酸32-42上，对应于RAS的效应区，第二个位于分子三分之二的羧基末端的其他地方。
Ras regulates proliferation and differentiation signals in cells, and activation of the protein can lead to malignant transformation. Activation of the related protein, Rho, affects cell morphology, and it has been suggested that it may also have some oncogenic potential. We show here that Rho does not induce a malignant phenotype in NIH3T3 cells but instead is a potent activator of actin stress fibre formation. The limited homology between Ras and Rho has enabled us to determine the amino acids specifying their different biological activities and GTPase-activating protein (GAP) protein sensitivities using chimeras. Rho substituted with amino acids 23-46 of Ras induces transformed foci in NIH3T3 monolayers, and we conclude that Ras has a single effector domain required for downstream signalling. Although mutational analysis of Rho has revealed that residues 32-42 are also essential for its biological activity, Ras substituted with amino acids 25-48 of Rho does not induce actin stress fibre formation. On the basis of these experiments, we propose that Rho may have two effector domains: one at amino acids 32-42 and corresponding to the effector region of Ras and the second located elsewhere in the carboxy-terminal two-thirds of the molecule.