Sieburth D S, Sun Q, Han M
Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, 80309-0347, USA.
Cell. 1998 Jul 10;94(1):119-30. doi: 10.1016/s0092-8674(00)81227-1.
We describe the identification and characterization of a novel gene, sur-8, that positively regulates Ras-mediated signal transduction during C. elegans vulval development. Reduction of sur-8 function suppresses an activated ras mutation and dramatically enhances phenotypes of mpk-1 MAP kinase and ksr-1 mutations, while increase of sur-8 dosage enhances an activated ras mutation. sur-8 appears to act downstream of or in parallel to ras but upstream of raf. sur-8 encodes a conserved protein that is composed predominantly of leucine-rich repeats. The SUR-8 protein interacts directly with Ras but not with the Ras(P34G) mutant protein, suggesting that SUR-8 may mediate its effects through Ras binding. A structural and functional SUR-8 homolog in humans specifically binds K-Ras and N-Ras but not H-Ras in vitro.
我们描述了一个新基因sur-8的鉴定和特征，该基因在秀丽隐杆线虫外阴发育过程中正向调节Ras介导的信号转导。sur-8功能的降低可抑制激活的ras突变，并显著增强mpk-1丝裂原活化蛋白激酶和ksr-1突变的表型，而sur-8剂量的增加则增强激活的ras突变。sur-8似乎作用于ras的下游或与之平行，但在raf的上游。sur-8编码一种保守蛋白，主要由富含亮氨酸的重复序列组成。SUR-8蛋白直接与Ras相互作用，但不与Ras(P34G)突变蛋白相互作用，这表明SUR-8可能通过与Ras结合来介导其作用。人类中一种结构和功能上与sur-8同源的蛋白在体外特异性结合K-Ras和N-Ras，但不结合H-Ras。
