Filaggrins

  • Beverly A. Dale
  • Katheryn A. Resing
  • Paul V. Haydock

Abstract

Filaggrins are a group of cationic, species-distinct proteins named for their ability to cause intermediate filament (IF) aggregation in vitro. Several types of intermediate filament associated proteins (IFAP) are now recognized and have been classified in a recent review (Steinert and Roop, 1988, and described elsewhere in this volume). Filaggrin was the first epidermal IFAP to be isolated, and is a readily studied example of this class of proteins. Various investigators have made significant progress on the protein structure and function. More recently, the cDNA has been used for studies of profilaggrin expression and gene structure.

Keywords

Stratum Corneum Granular Layer Epidermal Differentiation Cornified Layer Keratin Filament 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Baden, H. P., Roths, S. I., Goldsmith, L. A., Baden, S. B., and Lee, L. D., 1974, Keratohyalin protein in disorders of keratinization, J. Invest. Dermatol. 62: 411–414.PubMedCrossRefGoogle Scholar
  2. Ball, R. C., Walker, G. K., and Bernstein, I. A., 1978, Histidine-rich proteins as molecular markers of epidermal differentiation, J. Biol. Chem. 253: 5861–5868.PubMedGoogle Scholar
  3. Chou, P. Y., and Fasman, G. D., 1978, Prediction of the secondary structure of proteins from their amino acid sequence, Adv. Enzymol. 47: 45–148.PubMedGoogle Scholar
  4. Dale, B. A., 1977, Purification and characterization of a basic protein from the stratum corneum of mammalian epidermis, Biochim. Biophys. Acta 491: 193–204.PubMedCrossRefGoogle Scholar
  5. Dale, B. A., and Ling, S. Y., 1979a, Evidence of a precursor form of stratum corneum basic protein in rat epidermis, Biochemistry 18: 3539–3546.PubMedCrossRefGoogle Scholar
  6. Dale, B. A., and Ling, S. Y., 1979b, Immunologic cross-reaction of stratum corneum basic protein and a keratohyalin granule protein, J. Invest. Dermatol. 72: 257–261.PubMedCrossRefGoogle Scholar
  7. Dale, B. A., Holbrook, K. A., and Steinert, P. M., 1978, Assembly of stratum corneum basic protein and keratin filaments in macrofibrils, Nature 276: 729–731.PubMedCrossRefGoogle Scholar
  8. Dale, B. A., Resing, K. A., and Lonsdale-Eccles, J. D., 1985a, Filaggrin: a keratin filament associated protein, Ann. N.Y. Acad. Sci. 455: 330–342.PubMedCrossRefGoogle Scholar
  9. Dale, B. A., Holbrook, K. A., Kimball, J. R., Hoff, M., and Sun, T.-T., 1985b, Expression of epidermal keratins and filaggrin during human fetal skin development, J. Cell Biol. 101: 1257–1269.PubMedCrossRefGoogle Scholar
  10. Dale, B. A., Holbrook, K. A., Fleckman, P., Kimball, J. R., Brumbaugh, S., and Sybert, V. P., 1990, Heterogeneity in Harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules, J. Invest. Dermatol. 94: (in press).Google Scholar
  11. Donella Deana, A., Meggio, F., and Pinna, L. A., 1981, Specificity of a rat liver protein phosphatase active on caseins phosphorylated by two cAMP-independent protein kinases, FEBS Lett. 125: 77–82.PubMedCrossRefGoogle Scholar
  12. Eisen, A. Z., Arndt, K. A., and Clark, W. A., 1964, The ultrastructural localization of acid phosphatase in human epidermis, J. Invest. Dermatol. 43: 319–326.PubMedGoogle Scholar
  13. Fisher, C., Haydock, P. V., and Dale, B. A., 1987, Localization of profilaggrin mRNA in newborn rat skin by in situ hybridization, J. Invest. Dermatol. 88: 661–664.PubMedCrossRefGoogle Scholar
  14. Fleckman, P., Dale, B. A., and Holbrook, K. A., 1985, Profilaggrin, a high-molecular-weight precursor of filaggrin in human epidermis and cultured keratinocytes, J. Invest. Dermatol. 85: 507–512.PubMedCrossRefGoogle Scholar
  15. Freinkel, R. K., and Traczyk, T. N., 1983, Acid hydrolases of the epidermis: Subcellular localization and relationship to cornification, J. Invest. Dermatol. 80: 441–446.PubMedCrossRefGoogle Scholar
  16. Fukuyama, K., and Epstein, W. L., 1966, Epidermal keratinization: Localization of isotopically labeled amino acids, J. Invest. Dermatol. 47: 551–560.PubMedGoogle Scholar
  17. Fukuyama, K., Marshburn, I., and Epstein, W. L., 1981, Histidine-rich protein in developing rat epidermis, Dev. Biol. 81: 201–207.PubMedCrossRefGoogle Scholar
  18. Hara, A., Kato, T., Sawada, H., Fukuyama, K., and Epstein, W. L., 1985, Characterization of Fe2+-activated acid phosphatase in rat epidermis, Comp. Biochem. Physiol. 82B: 269–274.Google Scholar
  19. Harding, C. R., and Scott, I. R., 1983, Histidine-rich proteins (filaggrins): Structural and functional heterogeneity during epidermal differentiation, J. Mol. Biol. 170: 651–673.PubMedCrossRefGoogle Scholar
  20. Hathaway, G. M., and Traugh, J. A., 1982, Casein kinases: Multipotential protein kinases, Curr. Top. Cell. Regul. 21: 101–127.PubMedGoogle Scholar
  21. Haugen-Scofield, J. A., Resing, K. A., and Dale, B. A., 1988, Characterization of an epidermal phosphatase specific for filaggrin phosphorylated by casein kinase II, J. Invest. Dermatol., 91: 553–559.PubMedCrossRefGoogle Scholar
  22. Haydock, P. V., and Dale, B. A., 1986, Repetitive structure of the profilaggrin gene as demonstrated using epidermal profilaggrin cDNA, J. Biol. Chem. 261: 12520–12525.PubMedGoogle Scholar
  23. Haydock, P. V., and Dale, B. A., 1989, Filaggrin, an intermediate filament associated protein: Sequence of a cDNA from rat and implications for species specific divergence, submitted for publication.Google Scholar
  24. Holbrook, K. A., Dale, B. A., Sybert, V. P., and Sagegiel, R. W., 1983, Epidermolytic hyperkeratosis: Ultrastructure and biochemistry of skin and amniotic fluid cells from two affected fetuses and a newborn infant, J. Invest. Dermatol. 80: 222–227.PubMedCrossRefGoogle Scholar
  25. Hoober, J. K., and Bernstein, I. A., 1966, Protein synthesis related to epidermal differentiation, Proc. Natl. Acad. Sci. USA 56: 594–601.PubMedCrossRefGoogle Scholar
  26. Hsu, S. M., Raine, L., and Fanger, H., 1981, Use of avidin-biotin-peroxidase complex (ABC) in immunoperioxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures, J. Histochem. Cytochem. 29: 577–580.PubMedCrossRefGoogle Scholar
  27. Ingebritsen, T. S., and Cohen, P., 1983, Protein phosphatases: Properties and role in cellular regulation, Science 221: 331–338.PubMedCrossRefGoogle Scholar
  28. Kanitakis, J., Ramirez-Bosca, A., Reano, A., Viac, J., Roche, P., and Thivolet, J., 1988, Filaggrin expression in normal and pathological skin, Virchows Arch. A 412: 375–382.CrossRefGoogle Scholar
  29. Kashima, M., Fukuyama, K., Mamoru, K., and Epstein, W. L., 1988, Limited proteolysis of high molecular weight histidine-rich protein of rat epidermis by epidermal proteinases, J. Invest. Dermatol. 90: 829–833.PubMedCrossRefGoogle Scholar
  30. Kuenzel, E. A., and Krebs, E. G., 1985, A synthetic peptide substrate specific for casein kinase II, Proc. Natl. Acad. Sci. USA 82: 737–741.PubMedCrossRefGoogle Scholar
  31. Lonsdale-Eccles, J. D., Haugen, J. A., and Dale, B. A., 1980, A phosphorylated keratohyalin-derived precursor of epidermal stratum corneum basic protein, J. Biol. Chem. 255: 2235–2238.PubMedGoogle Scholar
  32. Lonsdale-Eccles, J. D., Teller, D. C., and Dale, B. A., 1982, Characterization of a phosphorylated form of the intermediate filament-aggregating protein filaggrin, Biochemistry 21: 5940–5948.PubMedCrossRefGoogle Scholar
  33. Lonsdale-Eccles, J. D., Resing, K. A., Meek, R. L., and Dale, B. A., 1984, High-molecular-weight precursor of epidermal filaggrin and hypothesis for its tandem repeating structure, Biochemistry 23: 1239–1245.PubMedCrossRefGoogle Scholar
  34. Lynley, A. M., and Dale, B. A., 1983, Characterization of human epidermal filaggrin, a histidine-rich, keratin filament-aggregating protein, Biochim. Biophys. Acta 744: 28–35.PubMedCrossRefGoogle Scholar
  35. Mäkinen, P.-L., and Mäkinen, K. K., 1981, Purification and properties of rat skin acid phosphatases, Int. J. Peptide Protein Res. 18: 352–369.CrossRefGoogle Scholar
  36. Mamrack, M. D., 1984, Protein phosphorylation and tumor promotion, in: Mechanisms of Tumor Promotion, Volume 2 (T. J. Slaga, ed.), CRC Press, Boca Raton, pp. 143–158.Google Scholar
  37. Meek, R. L., Lonsdale-Eccles, J. D., and Dale, B. A., 1983, Epidermal filaggrin is synthesized on a large messenger ribonucleic acid as a high-molecular-weight precursor, Biochemistry 22: 4867–4871.PubMedCrossRefGoogle Scholar
  38. Moll, R., Moll, I., and Wiest, W., 1983, Changes in the pattern of cytokeratin polypeptides in epidermis and hair follicles during skin development in human fetuses, Differentiation 23: 170–178.CrossRefGoogle Scholar
  39. Murozuka, T., Fukuyama, K., and Epstein, W. L., 1979, Immunochemical comparison of histidine-rich protein in keratohyalin granules and cornified cells, Biochim. Biophys. Acta 579: 334–345.PubMedCrossRefGoogle Scholar
  40. Ogawa, H., Hattori, M., and Ishibushi, Y., 1979, Abnormal fibrous protein isolated from the stratum comeum of a patient with bullous congenital ichthyosiform erythroderma (BCIE), Arch. Dermatol. Res. 266: 109–116.PubMedCrossRefGoogle Scholar
  41. Ramsden, M., Loehren, D., and Balmain, A., 1983, Identification of rapidly labeled 350k histidine-rich protein in neonatal mouse epidermis, Differentiation 23: 243–249.PubMedCrossRefGoogle Scholar
  42. Reaven, E. P., and Cox, A. J., Jr., 1963, The histochemical localization of histidine in the human epidermis and its relationship to zinc binding, Cytochemistry 11: 782–790.CrossRefGoogle Scholar
  43. Resing, K. A., Walsh, K. A., and Dale, B. A., 1984, Identification of two intermediates during processing of profilaggrin to filaggrin in neonatal mouse epidermis, J. Cell Biol. 99: 1372–1378.PubMedCrossRefGoogle Scholar
  44. Resing, K. A., Dale, B. A., and Walsh, K. A., 1985, Multiple copies of phosphorylated filaggrin in epidermal profilaggrin demonstrated by analysis of tryptic peptides, Biochemistry 24: 4167–4175.PubMedCrossRefGoogle Scholar
  45. Resing, K. A., Haugen-Scofield, J. A., Mamrack, M. C., and Dale, B. A., 1987, Use of filaggrin as a model substrate for epidermal kinases and phosphatases, in: Processes in Cutaneous Epidermal Differentiation (I. A. Bernstein and T. Hirone, eds.), Praeger Scientific, New York, pp. 165–185.Google Scholar
  46. Resing, K. A., Al-Alawi, N., and Dale, B. A., 1988, Purification of six nucleotide-independent kinases which phosphorylate an intermediate filament associated protein, filaggrin, Faseb J. 2: A1759.Google Scholar
  47. Resing, K. A., Walsh, K. A., and Dale, B. A., 1989, Identification of proteolytic cleavage sites in the conversion of profilaggrin to filaggrin in mammalian epidermis, J. Biol. Chem. 264: 1837–1846.PubMedGoogle Scholar
  48. Roop, D. R., Hawley-Nelson, P., Cheng, C. K., and Yuspa, S. H., 1983, Keratin gene expression in mouse epidermis and cultured epidermal cells, Proc. Natl. Acad. Sci. USA 80: 716–720.PubMedCrossRefGoogle Scholar
  49. Roop, D. R., Cheng, C. K., Toftgard, R., Stanley, J. R., Steinert, P. M., and Yuspa, S. H., 1985, The use of cDNA clones and monospecific antibodies as probes to monitor keratin gene expression, Ann. N.Y. Acad. Sci. 455: 426–435.PubMedCrossRefGoogle Scholar
  50. Rothnagel, J. A., and Steinert, P. M., 1988, Structure of the mouse filaggrin gene: characterization of its repeating structure and a comparison of the gene from different strains of mice, J. Cell Biol. 107: 250a.Google Scholar
  51. Rothnagel, J. A., Mehrel, T., Idler, W. W., Roop, D. R., and Steinert, P. M., 1987, The gene for mouse epidermal filaggrin precursor: Its partial characterization, expression, and sequence of a repeating filaggrin unit, J. Biol. Chem. 262: 15643–15648.PubMedGoogle Scholar
  52. Scott, I. R., and Harding, C. R., 1981, Studies on the synthesis and degradation of a high molecular weight, histidine-rich phosphoprotein from mammalian epidermis, Biochim. Biophys. Acta 669: 65–78.PubMedCrossRefGoogle Scholar
  53. Scott, I. R., and Harding, C. R., 1982, Histidine-rich proteins: Synthesis and post-translational modifications during epidermal differentiation, Biochem. Soc. Trans. 9: 1981–1982.Google Scholar
  54. Scott, I. R., and Harding, C. R., 1986, Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment, Dev. Biol., 115: 84–92.PubMedCrossRefGoogle Scholar
  55. Scott, I. R., Harding, C. R., and Barrett, J. G., 1982, Histidine rich protein of the keratohyaline granules: Source of the free amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum, Biochim. Biophys. Acta 719: 110–117.PubMedCrossRefGoogle Scholar
  56. Sibrack, L. A., Gray, R. H., and Bernstein, I. A., 1974, Localization of the histidine-rich protein in keratohyalin: A morphologic and macromolecular marker in epidermal differentiation, J. Invest. Dermatol. 62: 394–405.PubMedCrossRefGoogle Scholar
  57. Steinert, P. M., and Roop, D. R., 1988, Molecular and cellular biology of intermediate filaments, Annu. Rev. Biochem. 57: 593–625.PubMedCrossRefGoogle Scholar
  58. Steinert, P. M., Idler, W. W., and Zimmerman, S. B., 1976, Self-assembly of bovine epidermal keratin filaments in vitro, J. Mol. Biol. 108: 547–567.PubMedCrossRefGoogle Scholar
  59. Steinert, P. M., Cantieri, J. S., Teller, D. C., Lonsdale-Eccles, J. D., and Dale, B. A., 1981, Characterization of a class of cationic proteins that specifically interact with intermediate filaments, Proc. Natl. Acad. Sci. USA 78: 4097–4101.PubMedCrossRefGoogle Scholar
  60. Sun, T.-T., Eichner, R., Nelson, W. G., Tseng, S. C. G., Weiss, R. A., Jarvinen, M., and Woodcock-Mitchell, J., 1983, Keratin classes: Molecular markers for different types of epithelial differentiation, J. Invest. Dermatol. 81: 109s–115s.PubMedCrossRefGoogle Scholar
  61. Sybert, V. P., Dale, B. A., and Holbrook, K. A., 1985, Ichthyosis vulgaris: Identification of a defect in synthesis of filaggrin correlated with an absence of keratohyaline granules, J. Invest. Dermatol. 84: 191–194.PubMedCrossRefGoogle Scholar
  62. Ugel, A. R., 1971, Studies on isolated aggregating oligoribonucleoproteins of the epidermis with histochemical and morphological characteristics of keratohyalin, J. Cell Biol. 49: 405–422.PubMedCrossRefGoogle Scholar
  63. Ullman, B., and Perlman, R. L., 1975, Purification and characterization of a phosphoprotein phosphatase from bovine adrenal cortex, Biochim. Biophys. Acta 403: 393–411.PubMedCrossRefGoogle Scholar
  64. Vallee, B. L., and Galdes, A., 1984, The metallobiochemistry of zinc enzymes, Adv. Enzymol. 56: 283–430.PubMedGoogle Scholar
  65. Voorhees, J. J., Chakrabarti, S. G., and Bernstein, I. A., 1968, The metabolism of “histidine-rich” protein in normal and psoriatic keratinization, J. Invest. Dermatol. 51: 344–354.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Beverly A. Dale
    • 1
  • Katheryn A. Resing
    • 2
  • Paul V. Haydock
    • 3
  1. 1.Departments of Oral Biology, Periodontics, Medicine/Dermatology, and BiochemistryUniversity of WashingtonSeattleUSA
  2. 2.Department of BiochemistryUniversity of WashingtonSeattleUSA
  3. 3.Departments of Periodontics and Medicine/DermatologyUniversity of WashingtonSeattleUSA

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