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.
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.
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006680:HLA Antigens / Q000235:genetics; D015789:HLA-A2 Antigen; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D010446:Peptide Fragments / Q000032:analysis; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis; D011494:Protein Kinases / Q000378:metabolism*; D013045:Species Specificity
D006680:HLA Antigens; D015789:HLA-A2 Antigen; D046911:Macromolecular Substances; D010446:Peptide Fragments; D010761:Phosphorus Radioisotopes; D010768:Phosphoserine; D011494:Protein Kinases