Truesdell G M, Jones C, Holt T, Henderson G, Dickman M B
Department of Plant Pathology, University of Nebraska-Lincoln, 68583, USA.
Mol Gen Genet. 1999 Aug;262(1):46-54. doi: 10.1007/s004380051058.
Ras is a low-molecular-weight guanine nucleotide (GDP/GTP)-binding protein that transduces signals for growth and differentiation in eukaryotes. In mammals, the importance of Ras in regulating growth is underscored by the observation that activating mutations in ras genes are found in many animal tumors. Colletorichum trifolii is a filamentous fungal pathogen of alfalfa which causes anthracnose disease. To investigate signaling pathways that regulate growth and development in this fungus, a gene encoding a Ras homolog (CT-Ras) was cloned from C. trifolii. CT-Ras exhibited extensive amino acid similarity to Ras proteins from higher and lower eukaryotes. A single amino acid change resulting in mutationally activated CT-Ras induced cellular transformation of mouse (NIH 3T3) fibroblasts and tumor formation in nu/nu mice. In Colletotrichum, mutationally activated CT-Ras induced abnormal hyphal proliferation and defects in polarized growth, and significantly reduced differentiation in a nutrient-dependent manner. These results show that C. trifolii Ras is a functional growth regulator in both mammals and fungi, and demonstrate that proper regulation of Ras is required for normal fungal growth and development.
Ras是一种低分子量鸟嘌呤核苷酸（GDP/GTP）结合蛋白，可转导真核生物中生长和分化的信号。在哺乳动物中，ras基因的激活突变在许多动物肿瘤中被发现，这一现象突出了Ras在调节生长方面的重要性。三叶草炭疽菌是苜蓿的一种丝状真菌病原体，可引起炭疽病。为了研究调节这种真菌生长和发育的信号通路，从三叶草炭疽菌中克隆了一个编码Ras同源物（CT-Ras）的基因。CT-Ras与高等和低等真核生物的Ras蛋白表现出广泛的氨基酸相似性。导致CT-Ras突变激活的单个氨基酸变化诱导了小鼠（NIH 3T3）成纤维细胞的细胞转化以及裸鼠中的肿瘤形成。在炭疽菌中，突变激活的CT-Ras诱导了异常的菌丝增殖和极性生长缺陷，并以营养依赖的方式显著降低了分化。这些结果表明，三叶草炭疽菌Ras在哺乳动物和真菌中都是一种功能性生长调节因子，并证明了Ras的适当调节是真菌正常生长和发育所必需的。
