HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of phosphorylation and segmentation in class i major histocompatibility complex gene structure

J Biol Chem. 1984 Nov 10;259(21):13504-10.


The heavy chain of the HLA-A2 antigen is phosphorylated by cyclic AMP-dependent protein kinase at two serine residues of the intracellular region. Limited proteolysis was performed on purified [32P]HLA-A2 antigens in order to define the sites of phosphorylation. Both of the phosphorylated serine residues are located in the carboxyl terminus of the heavy chain; one is encoded by exon 5, while the other is encoded by exon 6. The phosphoserine encoded by exon 5 is part of the conserved sequence Arg-Arg-Lys-Ser-Ser. This protein sequence contains the proper arrangement of amino acids for recognition and phosphorylation by the catalytic subunit of cyclic AMP-dependent protein kinase. In the murine class I antigens (H-2), exon 5 encodes a similar sequence of basic residues followed by one intervening residue and a threonine rather than a serine residue in the last amino acid position. A composite figure is presented that compares the carboxyl-terminal sequences of human and murine class I antigens and illustrates the known sites of phosphorylation recognized by various kinases. Each site of phosphorylation in the carboxyl terminus is contained within a conserved protein sequence encoded by one of the three exons. A separation and preservation of unique sites of phosphorylation could explain why there is segmentation in the genomic arrangement of class I molecules.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • HLA Antigens* / genetics
  • HLA-A2 Antigen
  • Humans
  • Lymphocytes / immunology
  • Macromolecular Substances
  • Major Histocompatibility Complex*
  • Mice
  • Peptide Fragments / analysis
  • Phosphorus Radioisotopes
  • Phosphorylation
  • Phosphoserine / analysis
  • Protein Kinases / metabolism*
  • Species Specificity


  • HLA Antigens
  • HLA-A2 Antigen
  • Macromolecular Substances
  • Peptide Fragments
  • Phosphorus Radioisotopes
  • Phosphoserine
  • Protein Kinases