Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation.
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.
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins; D015321:Gene Rearrangement; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011946:Receptors, Antigen / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C064655:V(D)J recombination activating protein 2; D016203:CDC2 Protein Kinase