ARAF
小结
ARAF是原癌基因，属于丝氨酸/苏氨酸蛋白激酶家族的RAF亚家族。ARAF参与从细胞膜到细胞核的促有丝分裂信号的转导，也可以调节TOR信号级联。与ARAF相关疾病包括Pallister-Killian综合征和Marinum分枝杆菌。ARAF最近因其致癌潜力而越来越受到关注。一例具有ARAF p.S214C突变的晚期肺腺癌患者，索拉非尼治疗实现了近乎完全的临床缓解，证实了其作为临床靶向用药标志物的潜力。这一发现使ARAF成为新的焦点，作为一种标志物，应该在癌症治疗中进行检测。
ARAF is a serine/threonine protein kinase and signaling component in the mitogen-activated protein (MAP)-kinase signaling pathway. ARAF is a member of the RAF kinase family, which also includes BRAF and CRAF. ARAF is involved in the transduction of mitogenic signals from the cell membrane to the nucleus, and may also regulate the TOR signaling cascade. ARAF is ubiquitously expressed, with the highest physiological levels found in the urogenital organs. Upon activation by RAS proteins, ARAF forms dimers with BRAF and CRAF, resulting in phosphorylation and activation of the downstream signaling effectors MEK and subsequently ERK. Activation of the RAS signaling cascade ultimately leads to increased cell growth and proliferation. ARAF activating mutations are found at low frequencies in cholangiocarcinomas, lung, uterine and histiocytic carcinomas. The most common oncogenic ARAF mutation impairs a phosphorylation site that negatively regulates RAS binding and ARAF activation, leading to hyperactivity of the MAP-kinase signaling pathway. ARAF-mutant cancers may be sensitive to RAF and MAPK family inhibitors, such as sorafenib.