Lin W C, Desiderio S
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Science. 1993 May 14;260(5110):953-9. doi: 10.1126/science.8493533.
Antigen receptor genes are assembled by site-specific DNA rearrangement. The recombination activator genes RAG-1 and RAG-2 are essential for this process, termed V(D)J rearrangement. The activity and stability of the RAG-2 protein have now been shown to be regulated by phosphorylation. In fibroblasts RAG-2 was phosphorylated predominantly at two serine residues, one of which affected RAG-2 activity in vivo. The threonine at residue 490 was phosphorylated by p34cdc2 kinase in vitro; phosphorylation at this site in vivo was associated with rapid degradation of RAG-2. Instability was transferred to chimeric proteins by a 90-residue portion of RAG-2. Mutation of the p34cdc2 phosphorylation site of the tumor suppressor protein p53 conferred a similar phenotype, suggesting that this association between phosphorylation and degradation is a general mechanism.
抗原受体基因通过位点特异性DNA重排进行组装。重组激活基因RAG-1和RAG-2对于这一过程（称为V(D)J重排）至关重要。现已表明，RAG-2蛋白的活性和稳定性受磷酸化调节。在成纤维细胞中，RAG-2主要在两个丝氨酸残基处被磷酸化，其中一个在体内影响RAG-2的活性。第490位残基的苏氨酸在体外被p34cdc2激酶磷酸化；在体内该位点的磷酸化与RAG-2的快速降解相关。RAG-2的一个90个残基的片段将不稳定性转移至嵌合蛋白。肿瘤抑制蛋白p53的p34cdc2磷酸化位点发生突变会产生类似的表型，这表明磷酸化与降解之间的这种关联是一种普遍机制。
