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. 1992 Mar 15;89(6):2096–2100. doi: 10.1073/pnas.89.6.2096

cDNA cloning of a liver isoform of the phosphorylase kinase alpha subunit and mapping of the gene to Xp22.2-p22.1, the region of human X-linked liver glycogenosis.

J J Davidson 1, T Ozçelik 1, C Hamacher 1, P J Willems 1, U Francke 1, M W Kilimann 1
PMCID: PMC48603  PMID: 1372435

Abstract

We have cloned cDNA molecules encoding another isoform of the alpha subunit of phosphorylase kinase (ATP:phosphorylase-b phosphotransferase, EC 2.7.1.38). Sequence comparison with the previously characterized muscle isoform reveals a pattern of highly conserved and variable domains and demonstrates that the isoforms are the products of distinct genes. In contrast to the muscle isoform gene, PHKA1, the gene of this additional isoform, PHKA2, is predominantly expressed in liver and other nonmuscle tissues. It was mapped to the distal short arm of the human X chromosome (Xp22.2-p22.1), the same region to which human X-linked liver glycogenosis due to phosphorylase kinase deficiency has been mapped. Thus, X-linked liver glycogenosis is probably caused by mutations affecting PHKA2.

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Selected References

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  1. Barnard P. J., Derry J. M., Ryder-Cook A. S., Zander N. F., Kilimann M. W. Mapping of the phosphorylase kinase alpha subunit gene on the mouse X chromosome. Cytogenet Cell Genet. 1990;53(2-3):91–94. doi: 10.1159/000132902. [DOI] [PubMed] [Google Scholar]
  2. Barton D. E., Yang-Feng T. L., Francke U. The human tyrosine aminotransferase gene mapped to the long arm of chromosome 16 (region 16q22----q24) by somatic cell hybrid analysis and in situ hybridization. Hum Genet. 1986 Mar;72(3):221–224. doi: 10.1007/BF00291881. [DOI] [PubMed] [Google Scholar]
  3. Bender P. K., Lalley P. A. I/Lyn mouse phosphorylase kinase deficiency: mutation disrupts expression of the alpha/alpha'-subunit mRNAs. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9996–10000. doi: 10.1073/pnas.86.24.9996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chamberlain J. S., VanTuinen P., Reeves A. A., Philip B. A., Caskey C. T. Isolation of cDNA clones for the catalytic gamma subunit of mouse muscle phosphorylase kinase: expression of mRNA in normal and mutant Phk mice. Proc Natl Acad Sci U S A. 1987 May;84(9):2886–2890. doi: 10.1073/pnas.84.9.2886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chrisman T. D., Jordan J. E., Exton J. H. Purification of rat liver phosphorylase kinase. J Biol Chem. 1982 Sep 25;257(18):10798–10804. [PubMed] [Google Scholar]
  6. Cohen P. T., Le Marchand Brustel Y., Cohen P. Regulation of glycogen phosphorylase and glycogen synthase by adrenalin in soleus muscle of phosphorylase-kinase-deficient mice. Eur J Biochem. 1981 Apr;115(3):619–625. doi: 10.1111/j.1432-1033.1981.tb06247.x. [DOI] [PubMed] [Google Scholar]
  7. Daegelen-Proux D., Alexandre Y., Dreyfus J. C. Phosphorylase kinase isoenzymes in deficient ICR/IAn mice. Eur J Biochem. 1978 Oct;90(2):369–375. doi: 10.1111/j.1432-1033.1978.tb12613.x. [DOI] [PubMed] [Google Scholar]
  8. De Bruijn W. C., Fernandes J., Huber J., Koster J. F. Liver glycogenosis. A biochemical and ultrastructural study. Pathol Eur. 1975;10(1):3–15. [PubMed] [Google Scholar]
  9. Francke U., Busby N., Shaw D., Hansen S., Brown M. G. Intrachromosomal gene mapping in man: assignment of nucleoside phosphorylase to region 14cen leads to 14q21 by interspecific hybridization of cells with a t(X;14) (p22;q21) translocation. Somatic Cell Genet. 1976 Jan;2(1):27–40. doi: 10.1007/BF01539240. [DOI] [PubMed] [Google Scholar]
  10. Francke U., Darras B. T., Zander N. F., Kilimann M. W. Assignment of human genes for phosphorylase kinase subunits alpha (PHKA) to Xq12-q13 and beta (PHKB) to 16q12-q13. Am J Hum Genet. 1989 Aug;45(2):276–282. [PMC free article] [PubMed] [Google Scholar]
  11. Francke U. Random X inactivation resulting in mosaic nullisomy of region Xp21.1----p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease. Cytogenet Cell Genet. 1984;38(4):298–307. doi: 10.1159/000132078. [DOI] [PubMed] [Google Scholar]
  12. Francke U., Yang-Feng T. L., Brissenden J. E., Ullrich A. Chromosomal mapping of genes involved in growth control. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):855–866. doi: 10.1101/sqb.1986.051.01.099. [DOI] [PubMed] [Google Scholar]
  13. Gross S. R., Mayer S. E. Characterization of the phosphorylase b to a converting activity in skeletal muscle extracts of mice with the phosphorylase b kinase deficiency mutation. J Biol Chem. 1974 Nov 10;249(21):6710–6718. [PubMed] [Google Scholar]
  14. Harmann B., Kilimann M. W. cDNA encoding a 59 kDa homolog of ribosomal protein S6 kinase from rabbit liver. FEBS Lett. 1990 Oct 29;273(1-2):248–252. doi: 10.1016/0014-5793(90)81096-7. [DOI] [PubMed] [Google Scholar]
  15. Harmann B., Zander N. F., Kilimann M. W. Isoform diversity of phosphorylase kinase alpha and beta subunits generated by alternative RNA splicing. J Biol Chem. 1991 Aug 25;266(24):15631–15637. [PubMed] [Google Scholar]
  16. Huijing F., Eicher E. M., Coleman D. L. Location of phosphorylase kinase (Phk) in the mouse X chromosome. Biochem Genet. 1973 Jun;9(2):193–196. doi: 10.1007/BF00487449. [DOI] [PubMed] [Google Scholar]
  17. Huijing F., Fernandes J. X-chromosomal inheritance of liver glycogenosis with phosphorylase kinase deficiency. Am J Hum Genet. 1969 May;21(3):275–284. [PMC free article] [PubMed] [Google Scholar]
  18. Jones T. A., da Cruz e Silva E. F., Spurr N. K., Sheer D., Cohen P. T. Localisation of the gene encoding the catalytic gamma subunit of phosphorylase kinase to human chromosome bands 7p12-q21. Biochim Biophys Acta. 1990 Jan 30;1048(1):24–29. doi: 10.1016/0167-4781(90)90017-v. [DOI] [PubMed] [Google Scholar]
  19. Kilimann M. W. Molecular genetics of phosphorylase kinase: cDNA cloning, chromosomal mapping and isoform structure. J Inherit Metab Dis. 1990;13(4):435–441. doi: 10.1007/BF01799500. [DOI] [PubMed] [Google Scholar]
  20. Kilimann M. W., Zander N. F., Kuhn C. C., Crabb J. W., Meyer H. E., Heilmeyer L. M., Jr The alpha and beta subunits of phosphorylase kinase are homologous: cDNA cloning and primary structure of the beta subunit. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9381–9385. doi: 10.1073/pnas.85.24.9381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lederer B., Van Hoof F., Van den Berghe G., Hers H. Glycogen phosphorylase and its converter enzymes in haemolysates of normal human subjects and of patients with type VI glycogen-storage disease. A study of phosphorylase kinase deficiency. Biochem J. 1975 Apr;147(1):23–35. doi: 10.1042/bj1470023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lyon J. B., Jr The X-chromosome and the enzymes controlling muscle glycogen: phosphorylase kinase. Biochem Genet. 1970 Feb;4(1):169–185. doi: 10.1007/BF00484028. [DOI] [PubMed] [Google Scholar]
  23. Meyer H. E., Meyer G. F., Dirks H., Heilmeyer L. M., Jr Localization of phosphoserine residues in the alpha subunit of rabbit skeletal muscle phosphorylase kinase. Eur J Biochem. 1990 Mar 10;188(2):367–376. doi: 10.1111/j.1432-1033.1990.tb15413.x. [DOI] [PubMed] [Google Scholar]
  24. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Proux D., Alexandre Y., Delain D., Dreyfus J. C. The isozymes of phosphorylase kinase in various mammalian tissues. Biochimie. 1974;56(11-12):1559–1564. doi: 10.1016/s0300-9084(75)80279-3. [DOI] [PubMed] [Google Scholar]
  26. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schimke R. N., Zakheim R. M., Corder R. C., Hug G. Glycogen storage disease type IX: benign glycogenosis of liver and hepatic phosphorylase kinase deficiency. J Pediatr. 1973 Dec;83(6):1031–1034. doi: 10.1016/s0022-3476(73)80544-x. [DOI] [PubMed] [Google Scholar]
  28. Willems P. J., Gerver W. J., Berger R., Fernandes J. The natural history of liver glycogenosis due to phosphorylase kinase deficiency: a longitudinal study of 41 patients. Eur J Pediatr. 1990 Jan;149(4):268–271. doi: 10.1007/BF02106291. [DOI] [PubMed] [Google Scholar]
  29. Willems P. J., Hendrickx J., Van der Auwera B. J., Vits L., Raeymaekers P., Coucke P. J., Van den Bergh I., Berger R., Smit G. P., Van Broeckhoven C. Mapping of the gene for X-linked liver glycogenosis due to phosphorylase kinase deficiency to human chromosome region Xp22. Genomics. 1991 Apr;9(4):565–569. doi: 10.1016/0888-7543(91)90347-h. [DOI] [PubMed] [Google Scholar]
  30. Zander N. F., Meyer H. E., Hoffmann-Posorske E., Crabb J. W., Heilmeyer L. M., Jr, Kilimann M. W. cDNA cloning and complete primary structure of skeletal muscle phosphorylase kinase (alpha subunit). Proc Natl Acad Sci U S A. 1988 May;85(9):2929–2933. doi: 10.1073/pnas.85.9.2929. [DOI] [PMC free article] [PubMed] [Google Scholar]

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