The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene. A clue to the solution of the P1/ P2/p puzzle.
Blood group P1/ P2 is a glycolipid antigen system for which the genetic mechanism has not yet been clarified. We analyzed the potential of the cloned Gb3/CD77 synthase to synthesize P1 antigen, because Gb3/CD77 and P1 share a common structure, Galalpha1,4Galbeta1,4Glc (NAc)-. L cell transfectants with Gb3/CD77 synthase cDNA expressed marginal levels of P1 on the cell surface but contained high levels of P1 in the cytoplasm. P2-type erythrocytes, which were serotyped as P2, also contained definite P1 antigen inside cells, although the amounts were lower than those of P1 cells. Only p erythrocytes lacked P1 antigen corresponding with function-losing mutations in the Gb3/CD77 synthase gene. Synthesis of P1 antigen from paragloboside in vitro was demonstrated using membrane fraction of the transfectants and a fusion enzyme with protein A. These results strongly suggested that P1 synthase is identical to Gb3/CD77 synthase and appear to propose a clue for the solution of the long-pending P1/ P2/p puzzle. The P1/ P2 difference might result from the difference in P1 quantity based on either different enzyme activity or the presence/absence of other enzyme modulators. Because P2 erythrocytes showed lower levels of Gb3/CD77 synthase mRNA than P1, 5'-upstream promoter regions were analyzed, resulting in the identification of two P2-specific homozygous mutations. Differences in the transcriptional regulation in erythrocytes might be a major factor determining P1/ P2.[1]References
- The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene. A clue to the solution of the P1/P2/p puzzle. Iwamura, K., Furukawa, K., Uchikawa, M., Sojka, B.N., Kojima, Y., Wiels, J., Shiku, H., Urano, T., Furukawa, K. J. Biol. Chem. (2003) [Pubmed]
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