EFFECT OF RAF FAMILY PROTEIN KINASES ON CELL PHYSIOLOGY

自从v-raf被确定为急性髓细胞癌的癌基因以来 转化逆转录病毒，3611-小鼠肉瘤病毒，有意义 在分子和功能方面取得了进展。 RAF蛋白的特性及其对细胞的影响 生理学。(1)c-raf-1的氨基末端截短版本 和A-RAF-1在体外和体内均有转化。(2)RAF蛋白 位于细胞质中的蛋白激酶与src有关吗？ 基因超家族和截短版本具有Ser/Thr特异性 蛋白激酶活性。此外，c-RAF和A-RAF显示出同源性 对蛋白激酶C的作用，不仅在C-末端的激活域，而且 也在N-末端推测的调控结构域。(3)英国皇家空军- 转化成纤维细胞释放转化生长因子(S) (转化生长因子)，在某些情况下表达转化生长因子-αmRNA，并且是 抑制胶原蛋白的合成。(4)使用美国国立卫生研究院的功能分析 显微注射ras抑制3T3细胞的生长 单抗或平板型反转体的转化 柯尔斯滕肉瘤病毒转化的成纤维细胞提示RAF 家族癌基因的作用独立于ras，或者通过信号 不涉及RAS的转导途径或RAF具有 RAS下游为正值。

Since the identification of v-raf as the oncogene of the acutely transforming retrovirus, 3611-murine sarcoma virus, significant progress has been made in the molecular and functional characterization of raf proteins and their effects on cell physiology. (1) Amino terminally truncated versions of c-raf-1 and A-raf-1 are transforming in vitro and in vivo. (2) raf proteins are cytoplasmically located protein kinases related to the src gene superfamily and truncated versions possess ser/thr-specific protein kinase activity. Moreover, c-raf and A-raf show homology to protein kinase C, not only in the C-terminal kinase domain, but also in the N-terminal putative regulatory domain. (3) raf- transformed fibroblasts release transforming growth factor(s) (TGF), express TGF- alpha mRNA in certain cases, and are inhibited in collagen synthesis. (4) Functional assays utilizing NIH 3T3 cells that are growth arrested by microinjection of ras monoclonal antibody or transformation of flat revertants of Kirsten sarcoma virus-transformed fibroblasts suggest that raf family oncogenes act independent of ras, either through a signal transduction pathway not involving ras or one in which raf has a positive downstream of ras.