Storm S M, Brennscheidt U, Sithanandam G, Rapp U R
Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21701-1013.
Crit Rev Oncog. 1990;2(1):1-8.
There are three active raf genes in man and at least two in Xenopus and Drosophila. The mammalian c- and A-raf genes have 16 coding exons, which span 40 and 20 kb, respectively. B-raf is larger and extends over greater than 46 kb. Human c-raf-1 maps to chromosome 3p25 and A-raf-1 to Xp21. c-raf-1 RNA is present in many tissues, while A-raf and B-raf expression is restricted. A- and c-raf encode cytoplasmic ser/thr protein kinases of 68 and 74 kDa, which contain three conserved regions (CR). CR1 and 2 are in the amino terminal half, CR1 comprises the presumed ligand binding site, and CR3 represents the carboxy terminal kinase domain. All three genes can be artificially activated by deletions, provided CR3 is preserved. However, only c-raf-1 occurs naturally in truncated versions, such as v-raf and v-mil in the acutely transforming retroviruses 3611-MSV and MH2. raf transformation can also be affected by point mutation, suggesting that this mechanism may activate c-raf-1 as an oncogene in carcinogenesis.
人类有三个活跃的raf基因，非洲爪蟾和果蝇中至少有两个。哺乳动物的c-raf基因和A-raf基因有16个编码外显子，分别跨越40 kb和20 kb。B-raf基因更大，跨越超过46 kb。人类c-raf-1基因定位于3号染色体p25区，A-raf-1基因定位于X染色体p21区。c-raf-1 RNA存在于许多组织中，而A-raf和B-raf的表达则受到限制。A-raf和c-raf编码68 kDa和74 kDa的细胞质丝氨酸/苏氨酸蛋白激酶，它们包含三个保守区域（CR）。CR1和CR2位于氨基末端的一半，CR1包含推测的配体结合位点，CR3代表羧基末端激酶结构域。只要保留CR3，所有这三个基因都可以通过缺失进行人工激活。然而，只有c-raf-1基因以截短形式自然存在，如急性转化逆转录病毒3611-MSV和MH2中的v-raf和v-mil。raf基因的转化也可能受点突变影响，这表明该机制可能在致癌过程中将c-raf-1激活为癌基因。
