DOMAINS INVOLVED IN REGULATION OF RAF ACTIVITY

涉及英国皇家空军活动监管的领域

• 批准号: 3838392
• 负责人: G FANNING-HEIDECKER
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838392
• 关键词: biological signal transduction; genetic regulation; human tissue; ligands; mitogens; molecular oncology; molecular site; neoplasm /cancer genetics; oncogenes; oncoproteins; phosphorylation; point mutation; protein kinase

The protein products of the raf gene family are serine/threonine protein kinases. Raf kinases are involved in relaying mitogenic signals from the cell surface to the nucleus. They consist of two functional domains, the amino-terminal regulatory half and the carboxy-terminal catalytic half. Upon stimulation, the phosphorylation level of Raf proteins increases with modification mostly occurring on serines, threonines, and in the case of some mitogens on tyrosines. The four major sites of serine phosphorylation on Raf-1 were mapped in collaboration with Dr. D. Morrison to positions 42, 259, 285 and 620. In addition, Thr268 is modified and tyrosine phosphorylation occurs either at position 340 or 232. Mutations altering site 42 confer a slightly activated phenotype, while mutations involving position 259 are overly activated, and those at position 620 cause a dominant negative phenotype. In addition to phosphorylation, which mostly occurs in the regulatory domain, the protein is also regulated by other factors, most likely the interaction with low molecular weight ligands. Mutations interfering with a cysteine array, also located in the regulatory half, result in activated Raf-1, suggesting that this structure might be responsible for this type of interaction.

raf基因家族的蛋白质产物是丝/苏蛋白 激酶。 Raf激酶参与从细胞中传递促有丝分裂信号。 细胞表面到细胞核。 它们由两个功能域组成， 氨基末端调节半和羧基末端催化半。 在刺激后，Raf蛋白的磷酸化水平随着时间的推移而增加。 修饰主要发生在丝氨酸、苏氨酸上， 酪氨酸上的有丝分裂原 丝氨酸的四个主要位点 Raf-1的磷酸化与D.莫里森 到位置42、259、285和620。 此外，Thr 268被修饰， 酪氨酸磷酸化发生在340或232位。 突变 改变位点42赋予轻微活化的表型，而突变 涉及位置259的那些被过度激活，而位于位置620的那些被过度激活， 导致显性阴性表型。 除了磷酸化， 主要发生在调节结构域，该蛋白质也 受其他因素的调节，最有可能的是与低分子的相互作用， 重量配体。 干扰半胱氨酸阵列的突变， 在调节的一半，导致激活Raf-1，这表明， 结构可能是这种类型的相互作用的原因。