Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • CDC2 Protein Kinase / metabolism
  • Cell Line
  • DNA-Binding Proteins*
  • Gene Rearrangement*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins
  • Phosphorylation
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptors, Antigen / genetics*
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Tumor Suppressor Protein p53 / genetics


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proteins
  • RAG2 protein, human
  • Rag2 protein, mouse
  • Receptors, Antigen
  • Recombinant Fusion Proteins
  • Tumor Suppressor Protein p53
  • V(D)J recombination activating protein 2
  • CDC2 Protein Kinase